Ferroptosis is an emerging form of programmed cell death triggered by iron-dependent lipid peroxidation. It is distinguished from other forms of cell death by its unique morphological changes and characteristic fine-tuned regulatory gene network. Since its pivotal involvement in the pathogenesis and therapeutic interventions of various diseases, such as malignant tumors, cardiovascular and cerebrovascular diseases, and traumatic disorders, has been well-established, ferroptosis has garnered significant attention in contemporary physiological and pathological research. For the advantage of alleviating the clinical symptoms and improving life quality, traditional Chinese medicine (TCM) holds a significant position in the treatment of these ailments. Moreover, increasing studies revealed that TCM compounds and monomers showed evident therapeutic efficacy by regulating ferroptosis via signaling pathways that tightly regulate redox reactions, iron ion homeostasis, lipid peroxidation, and glutathione metabolism. In this paper, we summarized the current knowledge of TCM compounds and monomers in regulating ferroptosis, aiming to provide a comprehensive review of disease management by TCM decoction, Chinese patent medicine, and natural products deriving from TCM through ferroptosis modulation. The formulation composition, chemical structure, and possible targets or mechanisms presented here offer valuable insights into the advancement of TCM exploration.

Osteosarcoma (OS) is a prevalent primary malignant bone tumor that lacks effective therapeutic interventions. Artesunate (ART) has been proved to have remarkable treatment effects on severe malaria and anti-tumor properties. This study aimed to investigate the anti-OS effects and underlying mechanisms of ART. The potential mechanisms of ART-mediated anti-OS activity were analyzed by using RNA sequencing, iron accumulation, lipid peroxidation, western blotting, and small interfering RNA (siRNA) transfection. In vivo, a xenograft mice model was adopted to explore the anticancer effect of ART. The present study revealed that ART significantly suppressed OS cell proliferation. Subsequent results suggested that ART exerted anti-OS activity mainly through the ferroptosis pathway. ART decreased the GSH/GSSG ratio, xCT and GPX4 expression, while increasing MDA and lipid peroxidation, which were reversed by Fer-1, DFO, 3-MA, and NCOA4 silencing. Mechanistically, ART upregulated the expression of TFR and DMT1, and triggered ferritinophagy by upregulating the expression of NCOA4, which increased Fe2+ accumulation and triggered ferroptosis. In addition, cytoplasmic iron further activated Mfrn2-mediated transportation of cytoplasmic free iron into the mitochondria, resulting in mitochondrial iron overload, eventually leading to lipid peroxidation and ferroptosis. Furthermore, in an OS xenograft mouse model, administration of ART inhibited tumor growth by ferroptosis. Collectively, our findings indicated that ART has the potential anti-OS capacity through NCOA4-mediated ferritinophagy, which might shed light on the future of OS therapy.

Artesunate, a derivative of artemisinin, has a variety of pharmacological effects. Its potential application in ischemic brain injury still largely unknown. This study investigated the therapeutic effect and pharmacological mechanism of artesunate in neuronal injury following cerebral ischemia, and explore the potential role of lysosomal function and cGAS-STING signaling pathway in ischemia injury and artesunate treatment. Studies in rat models have revealed that artesunate can ameliorate neuronal injury and improve learning and memory function following ischemic insults. Furthermore, both in vivo and in vitro studies have confirmed that artesunate can protect neural cells from ischemic injury-induced cell death. Mechanistically, artesunate appears to exert its neuroprotective actions by activating lysosomal function and inhibiting the cGAS-STING pathway-mediated inflammatory response. Our findings provide valuable insights into the therapeutic effects of artesunate exerting a neuroprotective role in chronic ischemic brain injury by activating lysosomal function, inhibiting the cGAS-STING pathway, and regulating the inflammatory response. This study offers a potential therapeutic strategy by regulating lysosome for the treatment of stroke and related neurological disorders.

Artesunate, a semisynthetic derivative of artemisinin, is not only recommended as the first-line drug for treating severe malaria but is also a significant member of Artemisinin-based Combination Therapies (ACTs), used in combination with other artemisinin derivatives for treating uncomplicated malaria. Beyond its potent anti-malarial activity, artesunate has garnered considerable attention for its pharmacological effects, which encompass broad-spectrum anti-tumor, anti-viral, and anti-inflammatory properties. It has collectively demonstrated superior drug tolerance, low toxicity, and mild side effects in cell line experiments in vitro, experimental animal models, and clinical drug researches, as a monotherapy or in combination with other agents. Investigating the pharmacological effects of artesunate will facilitate the exploration of novel drug applications and enhance the comprehensive clinical applications.

TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target protein that has critical roles in glycolysis and redox balance. The reports about the effect of TIGAR on prognosis and its biological role in hepatocellular carcinoma (HCC) are limited.

A total of 386 patients with HCC who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. Additionally, the regulation of malignant activity and ferroptosis by TIGAR was investigated in vitro.

Patients were divided into TIGAR-positive (n = 80, 20.7%) and -negative (n = 306, 79.3%) groups. TIGAR positivity was significantly correlated with lower albumin, higher α-fetoprotein/ des-gamma-carboxyprothrombin, larger tumor size/number of tumors, and greater proportions of BCLC staging C/single nodular type/poor differentiation/microscopic vascular invasion/microscopic intrahepatic metastasis. In multivariate analysis, TIGAR positivity was an independent prognostic factor (p < 0.0001). In addition, TIGAR positivity was significantly associated with a smaller number of cluster of differentiation (CD) 8-positive T cells (p = 0.0450), larger number of CD68-positive macrophages (p = 0.0058), larger number of programmed death-ligand 1-positive cases (p = 0.0002), and larger number of vessels that encapsulate tumor cluster-positive cases (p = 0.0004). In vitro, TIGAR knockdown decreased cell motility and induced ferroptosis. TIGAR knockdown inhibited the phosphorylation of adenosine monophosphate-activated protein kinase and acetyl-CoA carboxylase. Ferroptosis induced by TIGAR knockdown was inhibited by liproxstatin and baicalein treatment. The combination of TIGAR knockdown and lenvatinib further induced ferroptosis.

High expression of TIGAR impacted the clinical outcome of HCC patients and TIGAR was associated not only with tumor microenvironment but also with resistance to ferroptosis.

Iron is a crucial mineral element within human cells, serving as a pivotal cofactor for diverse biological enzymes. Ferritin plays a crucial role in maintaining iron homeostasis within the body through its ability to sequester and release iron. Ferritinophagy is a selective autophagic process in cells that specifically facilitates the degradation of ferritin and subsequent release of free iron, thereby regulating intracellular iron homeostasis. The nuclear receptor coactivator 4 (NCOA4) serves as a pivotal regulator in the entire process of ferritinophagy, facilitating its binding to ferritin and subsequent delivering to lysosomes for degradation, thereby enabling the release of free iron. The free iron ions within the cell undergo catalysis through the Fenton reaction, resulting in a substantial generation of reactive oxygen species (ROS). This process induces lipid peroxidation, thereby stimulating a cascade leading to cellular tissue damage and subsequent initiation of ferroptosis. Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of emotional memory and cognitive function, accompanied by mental and behavioral aberrations. The pathology of the disease is characterized by aberrant deposition of amyloid β-protein (Aβ) and hyperphosphorylated tau protein. It has been observed that evident iron metabolism disorders and accumulation of lipid peroxides occur in AD, indicating a significant impact of ferritinophagy and ferroptosis on the pathogenesis and progression of AD. This article elucidates the process and mechanism of ferritinophagy and ferroptosis, investigating their implications in AD to identify novel targets for therapeutic intervention.

Resistant strains of Plasmodium spp. pose a great threat to healthcare. Drug repurposing is a smart, and an effective way to look for new alternatives for different ailments including malaria. Protein tyrosine kinases (PTKs) play a crucial role in growth, maturation as well as differentiation of Plasmodium and this study explores antimalarial activity of PTKs inhibitor gefitinib using in silico and experimental approaches. The drug showed considerable inhibitory activity against P. falciparum 3D7 (IC50 0.49 µg/mL) and RKL-9 (IC50 0.83 µg/mL) strains. Isobologram analysis revealed substantial synergism between gefitinib and artesunate. Gefitinib illustrated highest negative D-score towards phosphoethanolamine methyltransferase followed by PfPK5 and CDPK1. Its acute toxicity was 4 g/kg. Gefitinib (100 mg/kg) exhibited a dose-dependent curative activity against P. berghei with 91.09% chemo-suppression and the combination of gefitinib 100 mg/kg and AS 50 mg/kg exhibited complete parasite clearance with no recrudescence which was also evidenced by cytokine analysis, biochemical as well as histopathological studies. At length, gefitinib illustrated considerable antiplasmodial action by targeting phosphoethanolamine methyltransferase, PfPK5 and CDPK1. The combination of gefitinib (100 mg/kg) and AS (50 mg/kg) holds promise for malaria treatment. Further, research is being done to evaluate its pharmacokinetic properties.

The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed. The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.

Glaucoma filtration surgery (GFS) effectively lowers intraocular pressure in glaucoma patients, but postoperative bleb fibrosis often leads to surgical failure. Artesunate (ART) has demonstrated antifibrotic potential; however, its clinical use is limited by poor solubility and rapid degradation. This study aimed to develop chitosan-ART nanoparticles (CS@ART NPs) to improve ART's therapeutic efficacy in preventing bleb fibrosis. CS@ART NPs were synthesized using an ionic gelation method for chitosan encapsulation. Their characterization, including analyses of morphology, hydrodynamic properties, surface charge, encapsulation efficiency, drug release kinetics, stability, chemical structure, and mucoadhesive interactions, was carried out using various techniques such as TEM, DLS, zeta potential analysis, HPLC, FT-IR, 1H-NMR, and adhesion assays. The antifibrotic effects were evaluated in a rabbit GFS model through subconjunctival injection. Histological analysis as well as immunohistochemistry for fibrosis markers α-SMA and fibronectin were detected. In vitro studies were conducted using human primary ocular fibroblasts stimulated with TGF-β1 to assess anti-inflammatory and anti-proliferative effects, measured by EdU incorporation, Western blot for signaling pathway components, and cytokine expression. CS@ART NPs exhibited a uniform size distribution (135.73 ± 0.90 nm), stable dispersion, high encapsulation efficiency (86.4%), and sustained drug release. In the GFS model, a single subconjunctival injection of CS@ART significantly reduced collagen deposition, as well as α-SMA and fibronectin expression at the surgical site. In vitro, CS@ART demonstrated superior antifibrotic effects with a significantly lower IC50 for inhibiting fibroblast proliferation compared to ART alone. Mechanically, CS@ART suppressed the Cyclin D1-CDK4/6, TGF-β1/SMAD, and PI3K/Akt signaling pathways. Additionally, CS@ART showed marked anti-inflammatory effects, reducing inflammatory cell infiltration and IL-6 expression. CS@ART NPs play a dual role both alleviate bleb fibrosis and inflammation after GFS as a promising therapeutic strategy for improving surgical outcomes in glaucoma patients.

Ferritinophagy, the selective autophagic degradation of ferritin to release iron, is emerging as a critical regulator of iron homeostasis and a key player in the pathogenesis of various liver diseases. This review comprehensively examines the mechanisms, regulation, and multifaceted roles of ferritinophagy in liver health and disease. Ferritinophagy is intricately regulated by several factors, including Nuclear Receptor Coactivator 4 (NCOA4), Iron regulatory proteins and signaling pathways such as mTOR and AMPK. These regulatory mechanisms ensure proper iron utilization and prevent iron overload, which can induce oxidative stress and ferroptosis. In liver diseases, ferritinophagy exhibits dual roles. In liver fibrosis, promoting ferritinophagy in hepatic stellate cells (HSCs) can induce cell senescence and reduce fibrosis progression. However, in non-alcoholic fatty liver disease (NAFLD), chronic ferritinophagy may exacerbate liver injury through iron overload and oxidative stress. In hepatocellular carcinoma (HCC), ferritinophagy can be harnessed as a novel therapeutic strategy by inducing ferroptosis in cancer cells. Additionally, ferritinophagy is implicated in drug-induced liver injury and sepsis-associated liver damage, highlighting its broad impact on liver pathology. This review also explores the crosstalk between ferritinophagy and other selective autophagy pathways, such as mitophagy and lipophagy, which collectively influence cellular homeostasis and disease progression. Understanding these interactions is essential for developing comprehensive therapeutic strategies targeting multiple autophagy pathways. In summary, ferritinophagy is a complex and dynamic process with significant implications for liver diseases. This review provides an in-depth analysis of ferritinophagy's regulatory mechanisms and its potential as a therapeutic target, emphasizing the need for further research to elucidate its role in liver health and disease.

Artesunate (ART), an artemisinin-derived semi-synthetic sesquiterpene lactone distinguished by its unique endoperoxide group, has become a cornerstone of clinical antimalarial therapy. Recent research has demonstrated its broad pharmacological profile, including its potent antimalarial, anti-inflammatory, anti-tumor, antidiabetic, immunomodulatory, and anti-fibrotic properties. These discoveries have significantly broadened the therapeutic scope of ART and offer new perspectives for its potential use in treating gastrointestinal disorders. Mechanistically, ART exerts significant therapeutic effects against diverse gastrointestinal pathologies-such as gastric ulcers, ulcerative colitis (UC), hepatic fibrosis (HF), gastric cancer, hepatocellular carcinoma, and colorectal cancer-via multimodal mechanisms, including cell cycle modulation, apoptosis induction, the suppression of tumor cell invasion and migration, proliferation inhibition, ferroptosis activation, and immune regulation. This review evaluates existing evidence on ART's therapeutic applications and molecular mechanisms in digestive diseases, intending to elucidate its clinical translation potential. ART emerges as a promising multi-target agent with significant prospects for improving the management of gastrointestinal disorders.

Ferroptosis is a regulated cell death mechanism distinct from apoptosis, autophagy, and necroptosis, marked by iron accumulation and lipid peroxidation. Since its identification in 2012, it has developed into a potential therapeutic target, especially concerning GI disorders like PC, HCC, GC, and CRC. This interest arises from the distinctive role of ferroptosis in the progression of diseases, presenting a new avenue for treatment where existing therapies fall short. Recent studies emphasize the promise of focusing on ferroptosis to fight GI cancers, showcasing its unique pathophysiological mechanisms compared to other types of cell death. By comprehending how ferroptosis aids in the onset and advancement of GI diseases, scientists aim to discover novel drug targets and treatment approaches. Investigating ferroptosis in gastrointestinal disorders reveals exciting possibilities for novel therapies, potentially revolutionizing cancer treatment and providing renewed hope for individuals affected by these tumors.

Temozolomide (TMZ) is a first-line therapeutic medication for melanoma. Nonetheless, it exhibits a relatively elevated toxicity profile, and falls short in terms of both effectiveness and median survival rate. Clinical research has demonstrated that the integration of traditional Chinese medicine (TCM) with chemotherapy in the treatment of melanoma can enhance efficacy and reduce toxicity. A TCM formula (SLE) containing Lonicera japonica Thunb. and Robinia pseudoacacia L. has shown anti-melanoma properties through the inhibition of STAT3 phosphorylation. In the genesis and advancement of melanoma, the STAT3 signaling pathway is essential.

The aim of this study was to evaluate the effect of SLE combined with TMZ (SLE/TMZ) in inhibiting melanoma, and to explore the contribution of inhibiting the STAT3 signaling pathway in this effect.

Both A375 cells and B16F10 tumor-bearing mice were used for in vitro and in vivo experiments, respectively. In vitro assays included CCK8, crystal violet staining, flow cytometry, qRT-PCR, and Western blotting. Animal experiment indicators included tumor volume, tumor weight, mouse weight, and the proportion of mouse immune cells.

SLE/TMZ inhibited the proliferation and growth of A375 cells, and also induced apoptosis. Additionally, SLE/TMZ synergistically inhibited tumor growth in the B16F10 melanoma mouse model and had immunomodulatory effects, increasing the proportion of Th, Tc, and NK cells and decreasing the proportion of MDSCs in the spleen of melanoma-bearing mice. qRT-PCR and Western blotting results confirmed that SLE/TMZ inhibited STAT3 phosphorylation and regulated its downstream factors, including Bcl2, Mcl1, CCND1, MYC, MMP2, MMP9, VEGFA, and FGF2. The inhibitory effect of SLE/TMZ on melanoma cell growth was considerably lessened when STAT3 was overexpressed at the cellular level.

Synergistic anti-melanoma effects of SLE/TMZ have been observed in animal and cellular models. One of the mechanisms of SLE/TMZ that underlies its anti-melanoma actions is inhibition of the STAT3 pathway. This work offers pre-clinical pharmacological backing for the advancement of SLE as a therapeutic agent to be used in conjunction with TMZ for the treatment of melanoma.

Artesunate can inhibit the proliferation of various tumor cells and has practical value in developing anti-tumor drugs. However, its biological activity against hepatocellular carcinoma is weak. The efficacy of its anti-tumor effect needs to be improved.

11 compounds of three types were designed and synthesized. Their antitumor activity was detected by MTT assay in vitro and subcutaneous xenograft model in vivo. Then, DCFH-DA probe detection and NAC intervention experiments were used to detect ROS levels. The ferroptosis inhibitor (Liproxstatin-1) was used to study the effect of compound 6c in inducing ferroptosis. Western blot was used to observe the expression of apoptosis-related proteins. The ability of 6c to induce apoptosis was detected by Annexin V-FITC/PI double staining and Hoechst 33342 staining experiment. The effect of 6c on cycle arrest was detected by flow cytometry. Molecular simulations of several hybrids with vascular endothelial growth factor receptor 2 (VEGFR-2) and Transferrin receptor protein 1 (TFR1) were performed using MOE molecular docking software.

A series of new artemisinin-4-(4-substituted phenoxy) pyridine derivatives were synthesized and their anticancer activities were tested in three lines of hepatocellular carcinoma (HCC) cells. Among the hybrid hits with anticancer activity, a representative 6c compound increased the reactive oxygen species (ROS) level in hepatocellular carcinoma cells and activated mitochondrial apoptosis and ferroptosis, leading to cell cycle arrest at G2/M phase. Molecular docking shows the binding of 6c compound to oncogenic vascular endothelial growth factor receptor 2 (VEGFR-2) and Transferrin receptor protein 1 (TFR1) that are overexpressed in malignant epithelial tumors.

Taken together, our identification of the promising compound 6c may hold developmental potential for therapy of hepatocellular carcinoma.

One of the most common tumors is hepatocellular carcinoma (HCC), and the prognosis for late-stage HCC is still not good. It is anticipated that improved outcomes would result from a deeper comprehension of the pathophysiology of HCC. Ferroptosis as a new discovered cell death type is linked to the progression of HCC and may be crucial for its detection, prevention, therapy, and prognosis. Numerous studies suggest that epigenetic alterations mediated by non-coding RNAs (ncRNA) might influence cancer cell susceptibility to ferroptosis. This study elucidates the processes of ferroptosis and delineates the paths by which ncRNAs influence HCC by modulating ferroptosis. Furthermore, it offers significant insights into ferroptosis-associated ncRNAs, intending to discover novel therapeutic approaches for HCC. It also explores innovative concepts for the future use of ncRNA-based ferroptosis-targeted therapeutics.

Hepatocellular carcinoma (HCC) is a major medical challenge due to its high incidence and poor prognosis. 5-Fluorouracil (5-FU), although extensively studied in the treatment of HCC and other solid tumors, has limited application as a first-line therapy for HCC due to its resistance and significant inter-patient variability. To address these issues, researchers have explored drug repurposing. One of our key findings in this endeavour was the potent anti-HCC effect of the natural product Salidroside (Sal) when co-administered with 5-FU. Sal was found to inhibit mitosis and promote cellular senescence in HCC cells via a mechanism distinct from 5-FU, specifically by inducing excessive mitophagy that led to cellular mitochondrial dysfunction. Importantly, YIPF5 was confirmed as a potential molecular target of Sal. This natural product modulated YIPF5-induced mitophagy and influenced both mitosis and senescence in HCC cells. The combination of Sal and 5-FU demonstrated significant therapeutic effects in a mouse HCC model. In conclusion, our study was not only in line with the innovative strategy of drug repurposing, but also important for drug design and natural product screening targeting the relevant pathways.

Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.

The dysregulation of ribosome biogenesis has been extensively identified in various cancers, making it emerge as a hallmark of malignant cells. This highlights the potential of targeting ribosome biogenesis as an effective approach for treating cancer patients. Although chemotherapy drugs including doxorubicin and cisplatin often target ribosome biogenesis to induce DNA damage or inhibit tumor cell proliferation, they are associated with significant side effects.

This study aims to reveal the novel role of artesunate (ART), a well-known antimalarial drug, in suppressing ribosome RNA biogenesis in ovarian cancer.

In this study, the inhibitory effects of ART on ovarian cancer were studied both in vitro and in vivo. The effects of ART on ribosome RNA biogenesis were detected by 5-ethynyl uridine staining, RT-qPCR, and western blotting. Drug affinity responsive target stability, mass spectrometry, molecular docking and western blotting were combined to identify ART molecular targets.

Ovarian cancer cells treated with ART exhibited significant reduction in nascent rRNA synthesis, accompanied by a remarkable down-regulation of pre-rRNA and mature rRNA expression. The inhibitory effect of ART on ribosome biogenesis subsequently impaired cell proliferation, cell migration and invasion, and induced apoptosis. In eukaryotes, ribosome RNA synthesis primarily occurs in the nucleus, involving processes such as rDNA transcription, pre-rRNA splicing and the assembly of ribosome precursors with ribosomal proteins, other closely-related proteins and small nucleolar RNAs. We observed that ART inhibited the nuclear translocation of FANCA through binding to FANCA protein, consequently leading to the inhibition of ribosome RNA synthesis. Moreover, knockdown of FANCA in ovarian tumor cells resulted in reduced rRNA transcription, suppressed cell proliferation and migration, and induced apoptosis which might be mediated through the inhibition of mTOR/RPS6 activity. In vivo studies using xenograft tumors in nude mice demonstrated that ART repressed the growth of established ovarian cancer tumors. Additionally, ART treatment significantly altered FANCA protein level in these tumors, especially suppressed its nuclear localization.

These findings establish ART as a potent inhibitor of ribosome biogenesis, presenting a promising therapeutic avenue for ovarian tumors with high FANCA expression or for cancer patients exhibiting abnormal activation of the mTOR-RPS6 pathway.

While higher therapeutic doses of toxic cardiac glycosides derived from Cerbera odollam are frequently employed in cases of suicide or homicide, ongoing research is investigating the potential anticancer properties of low-concentration extracts obtained from the fruits of C. odollam. The present study aimed to determine the enhanced anticancer effects and minimize potential side effects of combining extracts from C. odollam fruits from Thailand with sorafenib against HCT116 and HepG2 cells.

The dried powder of fresh green fruits of C. odollam was fractionated, and its phytochemical contents, including total cardiac glycosides, phenolics, flavonoids, and triterpenoids, were quantified. The cytotoxic effects of these fractions were evaluated against HCT116 and HepG2 cells using the MTT assay. The fractions showing the most significant response in HCT116 and HepG2 cells were subsequently combined with sorafenib to examine their synergistic effects. Apoptosis induction, cell cycle progression, and mitochondrial membrane potential (MMP) were then assessed. The underlying mechanism of the apoptotic effect was further investigated by analyzing reactive oxygen species (ROS) generation and the expression levels of antioxidant proteins.

Phytochemical analysis showed that C. odollam-ethyl acetate fraction (COEtOAc) was rich in cardiac glycosides, phenolics, and flavonoids, while the dichloromethane fraction (CODCM) contained high levels of triterpenoids and saponins. Following 24 h treatment, HCT116 showed the most significant response to COEtOAc, while HepG2 responded well to CODCM with IC50 values of (42.04 ± 16.94) μg/mL and (123.75 ± 14.21) μg/mL, respectively. Consequently, COEtOAc (20 μg/mL) or CODCM (30 μg/mL), both administered at sub-IC50 concentrations, were combined with sorafenib at 6 μmol/L for HCT116 cells and 2 μmol/L for HepG2 cells, incubated for 24 h. This combination resulted in a significant suppression in cell viability by approximately 50%. The combination of treatments markedly enhanced apoptosis, diminished MMP, and triggered G0/G1 phase cell cycle arrest compared to the effects of each treatment administered individually. Concurrently, increased formation of ROS and decreased expression of the antioxidant enzymes superoxide dismutase 2 and catalase supported the proposed mechanism of apoptosis induction by the combination treatment. Importantly, the anticancer effect demonstrated a specific targeted action with a favorable safety profile, as evidenced by HFF-1 cells displaying IC50 values 2-3 times higher than those of the cancer cells.

Utilizing sub-IC50 concentrations of COEtOAc or CODCM in combination with sorafenib can enhance targeted anticancer effects beyond those achieved with single-agent treatments, while mitigating opposing side effects. Future research will focus on extracting and characterizing active constituents, especially cardiac glycosides, to enhance the therapeutic potential of anticancer compounds derived from toxic plants.

Ferroptosis is a novel form of oxidative cell death, in which highly expressed unsaturated fatty acids on the cell membrane are catalyzed by divalent iron or ester oxygenase to promote liposome peroxidation. This process reduces cellular antioxidant capacity, increases lipid reactive oxygen species, and leads to the accumulation of intracellular ferrous ions, which disrupts intracellular redox homeostasis and ultimately causes oxidative cell death. Studies have shown that ferroptosis induces an immune response that has a dual role in liver disease, ferroptosis also offers a promising strategy for precise cancer therapy. Ferroptosis regulators are beneficial in maintaining cellular homeostasis and tissue health, have shown efficacy in treating diseases of the hepatic system. However, the mechanisms of action and molecular regulatory pathways of ferroptosis in hepatocellular carcinoma (HCC) have not been fully elucidated. Therefore, deciphering the role of ferroptosis and its mechanisms in HCC progression is crucial for treating the disease. In this review, we introduce the morphological features and biochemical functions of ferroptosis, outline the molecular regulatory pathways of ferroptosis, and highlights the therapeutic potential of ferroptosis inhibitors and modulators to target it in HCC.

Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. Asiatic acid (AA) is a natural triterpene, which is recognized as effect of antioxidant and antitumor. Sorafenib (Sor), an orally target drug, has been applicate for the HCC therapy. However, the synergistic effect of AA and Sor on human HCC is still unclear. Here, we explore the effect of combined treatment with AA and Sor in the HCC cell line SK-HEP-1 and HepG2. Compared with treating alone, our results demonstrated that AA combined with Sor synergistically inhibited proliferative rates in MTT assay and colony formation assay. We also found that AA combined with Sor in HCC cells strongly caused cell cycle arrest in G0/G1 phase and affected the protein level of cyclin D1 and SKP2. Furthermore, combination treatment strongly enhanced ferroptosis through cellular accumulation of iron ions, lipid peroxidation, and ferroptosis-related proteins (GPX4 and FTH1) in HCC cells. In addition, the combined treatment resulted in higher phosphorylation of JNK1/2 in the promotion of ferroptosis than drug treatment alone. These results indicate that AA combined with Sor synergistically improved ferroptosis in HCC cells through the regulation of JNK1/2 signaling. Taken together, the combinatorial strategy may serve as the potential treatment in HCC.

The emergence of sorafenib resistance has become a predominant impediment and formidable dilemma in the therapeutic approach for hepatocellular carcinoma (HCC). Although the approval of next-generation drugs as alternatives to sorafenib is a significant development, the concurrent use of inhibitors that target additional key molecular pathways remains an effective strategy to mitigate the acquisition of resistance. Here, we identified Glutathione S-Transferase Alpha 1 (GSTA1) as a critical modulator of sorafenib resistance (SR) in hepatocellular carcinoma (HCC) based on our findings from experiments conducted on recurrent liver cancer tissues, xenograft mouse models, organoids, and sorafenib-resistant cells. Elevated GSTA1 levels are strongly associated with adverse clinical prognoses. The knockout of GSTA1 reinstates sorafenib sensitivity, whereas its overexpression attenuates drug efficacy. Mechanistically, GSTA1 enhances the accumulation of lipid peroxides and suppresses ferroptosis by exerting its peroxidase function to regulate the SR. Notably, the upregulation of GSTA1 expression is mediated by the transcription factor CTNNB1 (β-catenin), resulting in the formation of a cytoplasmic complex between GSTA1 and CTNNB1. This complex facilitates the nuclear translocation of CTNNB1, establishing a positive feedback loop. The combined use of GSTA1 and CTNNB1 inhibitors demonstrated synergistic anti-tumour effects through the induction of ferroptosis both in vitro and in vivo. Our findings reveal a novel regulatory role of the GSTA1/CTNNB1 axis in ferroptosis, suggesting that targeting GSTA1 and CTNNB1 could be a promising strategy to circumvent sorafenib resistance in HCC.

Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.

Liver cancer represents a multifactorial, multistage, and intricately progressive malignancy. Over the past decade, artesunate (ART), initially renowned for its anti-malarial efficacy, has been the focus of over 3000 studies uncovering its diverse pharmacological actions, including anti-inflammatory, immunoregulatory, metabolic regulatory, anti-fibrotic, and anti-cancer properties. This review highlights ART's role in the multistep progression from hepatitis to cancer and its underlying regulatory mechanisms, revealing signal transducer and activator of transcription 3 (STAT3) and ferroptosis (a novel form of programmed cell death) as promising therapeutic targets. ART demonstrates efficacy in inhibiting hepatitis virus infections, modulating inflammation, and facilitating recovery from inflammatory processes. During stages of hepatic fibrosis or cirrhosis, ART reverses fibrotic and cirrhotic changes by suppressing hepatic stellate cell activity, regulating inflammatory pathways, inhibiting hematopoietic stem cell proliferation, and inducing ferroptosis. Additionally, ART hinders hepatocellular carcinoma (HCC) cell proliferation, invasion, and metastasis, induces apoptosis and autophagy, combats drug resistance, and enhances chemosensitivity. Collectively, ART exhibits multi-step actions across multiple targets and signaling pathways, highlighting its potential as a clinical candidate for the prevention and treatment of liver cancer, from hepatitis and hepatic fibrosis to advanced HCC.

Hepatocellular carcinoma (HCC) is a formidable disease, distinguished by its high aggressiveness and dismal outcomes. Although leucine aminopeptidase (LAP) has been widely employed as a biomarker in biological imaging of HCC, it is still susceptible to interference from false-positive signals activated in injured liver tissues. In this study, based on the significant difference of GSH levels in alcohol-damaged liver tissues and tumor tissues, a dual-tandem activatable probe (PCLT) was designed for differential diagnosis and treatment guidance of HCC by near-infrared fluorescence (NIRF) imaging. This probe comprised a dual-locked hemicyanine dye decorated with a tetraethylene glycol chain and dual-recognition unit of glutathione (GSH) and LAP, which could be sequentially cleaved by GSH and LAP to restore its NIRF signal. PCLT excellently discriminated orthotopic HCC from ALI far earlier (7 days) than histological analysis (28 days) and exhibited higher specificity toward early orthotopic HCC than the single-locked probe (PCL). In addition, PCLT is capable of accurately delineating the tumor contour, assisting in surgical resection of HCC tumors under fluorescence visualization, and noninvasively assessing the antitumor effect of HCC chemotherapy during ferroptosis, thereby presenting promising clinical implications for clinical diagnosis and therapy of HCC.

Artesunate (ART) has been implicated in regulating the many processes of liver injury, but its roles in liver regeneration still need to be illustrated.

In the present study, ART was used to pretreat hepatocyte cell line NCTC1469 to study the effect of ART on hepatocyte proliferation in vitro. Furthermore, the potency of ART as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice.

ART concentration-dependently promoted hepatocyte proliferation and reduced apoptosis. Cell cycle and Ki-67 immunohistochemical analyses demonstrated that ART supplementation promoted the proliferation of hepatocytes and accelerated liver regeneration. Our results provided evidence that ART improved liver function in a dose-dependent manner, as indicated by decreased serum alanine aminotransferase, aspartate aminotransferase, and increased albumin, and hepatocyte growth factor levels in PH mice. Meanwhile, ART promoted the PI3K/Akt/mTOR signaling in NCTC1469 cells and liver tissue of PH mice. In addition, PI3K inhibitor LY294002 blocked the promotion effect of ART on hepatocyte proliferation and cell cycle progression.

ART promoted hepatocyte proliferation via activation of the PI3K/Akt/mTOR pathway, which was beneficial to liver regeneration of PH-induced liver injury.

Artesunate (ART) is a classic antimalarial drug with high efficiency, low toxicity and tolerance. It has been shown to be safe and has good anti-tumor effect. Existing clinical studies have shown that the anti-tumor mechanisms of ART mainly include inducing apoptosis and autophagy of tumor cells, affecting tumor microenvironment, regulating immune response, overcoming drug resistance, as well as inhibiting tumor cell proliferation, migration, invasion, and angiogenesis. ART has been proven to fight against lung cancer, hepatocarcinoma, lymphoma, multiple myeloma, leukemia, colorectal cancer, ovarian cancer, cervical cancer, malignant melanoma, oral squamous cell carcinoma, bladder cancer, prostate cancer and other neoplasms. In this review, we highlight the effects of ART on various tumors with an emphasis on its anti-tumor mechanism, which is helpful to propose the potential research directions of ART and expand its clinical application.

Hepatocellular carcinoma (HCC) is the sixed most common malignant tumor in the world. The study for HCC is mired in the predicament confronted with the difficulty of early diagnosis and high drug resistance, the survival rate of patients with HCC being low. Ferroptosis, an iron-dependent cell death, has been discovered in recent years as a cell death means with tremendous potential to fight against cancer. The in-depth researches for iron metabolism, lipid peroxidation and dysregulation of antioxidant defense have brought about tangible progress in the firmament of ferroptosis with more and more results showing close connections between ferroptosis and HCC. The potential role of ferroptosis has been widely used in chemotherapy, immunotherapy, radiotherapy, and nanotherapy, with the development of various new drugs significantly improving the prognosis of patients. Based on the characteristics and mechanisms of ferroptosis, this article further focuses on the main signaling pathways and promising treatments of HCC, envisioning that existing problems in regard with ferroptosis and HCC could be grappled with in the foreseeable future.

Gout is an autoinflammatory disorder characterized by the accumulation of monosodium urate crystals in joints and other tissues, representing the predominant type of inflammatory arthritis with a notable prevalence and propensity for severe outcomes. The NLRP3 inflammasome, a member of the pyrin domain-containing NOD-like receptor family, exerts a substantial impact on both innate and adaptive immune responses and serves as a pivotal factor in the pathogenesis of gout. In recent years, there has been significant academic and industrial interest in the development of NLRP3-targeted small molecule inhibitors as a promising therapeutic approach for gout. To assess the advancements in NLRP3 inflammasome inhibitors for gout treatment, this review offers a comprehensive analysis and evaluation of current clinical candidates and other inhibitors targeting NLRP3 inflammasome from a chemical structure standpoint, with the goal of identifying more efficacious options for clinical management of gout.

The most widespread type of liver cancer, HCC, is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis of patients with HCC, driving the search for agents that might target novel cell death pathways. Ferroptosis, a form of iron-mediated nonapoptotic cell death, has gained considerable attention as a potential target for cancer therapy, especially in HCC. The role of ferroptosis in HCC is complex and diverse. On one hand, ferroptosis can contribute to the progression of HCC through its involvement in both acute and chronic liver conditions. In contrast, having ferroptosis affect HCC cells might be desirable. This review examines the role of ferroptosis in HCC from cellular, animal, and human perspectives while examining its mechanisms, regulation, biomarkers, and clinical implications.

Ferroptosis inducers (FIN) have a key role in cancer therapy and provide novel and innovative treatment strategies. Although many researchers have performed FIN screening of synthetic compounds, studies on the identification of FIN from natural products are limited, particularly in the field of drug development and combination therapy. In this review, this gap was addressed by comprehensively summarizing recent studies on ferroptosis. The causes of ferroptosis were categorized into driving and defensive factors, elucidating key pathways and targets. Next, through summarizing research on natural products that induce ferroptosis, the study elaborated in detail on the natural products that have FIN functions. Their discovery and development were also described and insight for clinical drug development was provided. In addition, the mechanisms of action were analyzed and potential combination therapies, resistance reversal and structural enhancements were presented. By highlighting the potential of natural products in inducing ferroptosis for cancer treatment, this review may serve as a reference for utilizing these compounds against cancer. It not only showed the significance of natural products but may also promote further investigation into their therapeutic effects, thus encouraging research in this field.

The natural product auraptene can influence tumor cell proliferation and invasion, but its effect on hepatocellular carcinoma (HCC) cells is unknown. Here, we report that auraptene can exert anti-tumor effects in HCC cells via inhibition of cell proliferation and ferroptosis induction. Auraptene treatment induces total ROS and lipid ROS production in HCC cells to initiate ferroptosis. The cell death or cell growth inhibition of HCC cells induced by auraptene can be eliminated by the ROS scavenger NAC or GSH and ferroptosis inhibitor ferrostatin-1 or Deferoxamine Mesylate (DFO). Mechanistically, the key ferroptosis defense protein SLC7A11 is targeted for ubiquitin-proteasomal degradation by auraptene, resulting in ferroptosis of HCC cells. Importantly, low doses of auraptene can sensitize HCC cells to ferroptosis induced by RSL3 and cystine deprivation. These findings demonstrate a critical mechanism by which auraptene exhibits anti-HCC effects via ferroptosis induction and provides a possible therapeutic strategy for HCC by using auraptene or in combination with other ferroptosis inducers.

rAj-Tspin, a soluble recombinant peptide from Apostichopus japonicus, can inhibit the integrin β1 (ITGB1)/FAK/AKT signaling pathway in hepatocellular carcinoma (HCC) via cell epithelial-mesenchymal transition (EMT) and apoptosis. Zyxin (ZYX) is a focal adhesion protein that is considered a novel mediator of EMT and apoptosis. However, the inhibitory mechanisms of rAj-Tspin in HCC and whether it is related to ZYX are unclear. We examined the antitumor effect of rAj-Tspin on the Huh7 human HCC cell line and on a nude mouse model generated via subcutaneous injection or orthotopic intrahepatic transplantation of Huh7 cells. Our results revealed that rAj-Tspin strikingly reduced the viability and promoted the apoptosis of Huh7 cells and inhibited HCC tumor growth in nude mice. rAj-Tspin inhibited ITGB1 and ZYX protein expression in vivo and in vitro in a dose-dependent manner. Mechanistically, the FAK/AKT signaling pathway and the proliferation and invasion of HCC cells were suppressed upon ITGB1 and ZYX knockdown. Moreover, the effect of ITGB1 overexpression on the growth of HCC cells was inhibited by rAj-Tspin. In contrast, the promoting effect of ITGB1 overexpression could be inhibited by ZYX knockdown. ZYX knockdown had no effect on ITGB1 expression. These findings suggest that ZYX is required for the indispensable role of ITGB1 in rAj-Tspin-alleviated HCC and provide an important therapeutic target for HCC. In summary, the anti-HCC effect of rAj-Tspin potentially involves the regulation of the ITGB1/ZYX/FAK/AKT pathway, which in turn impacts EMT and apoptosis.

Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment.

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc- -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases.

This comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases.

We searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as "ferroptosis","respiratory diseases","chronic obstructive pulmonary disease","bronchial asthma","acute lung injury","pulmonary fibrosis","lung cancer","traditional Chinese medicine","traditional Chinese medicine compound","monomer", and "natural product" to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review).

TCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc- -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1.

TCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.

To alleviate bone loss, most current drugs target osteoclasts. Saikosaponin A (Ssa), a triterpene saponin derived from Bupleurum falcatum (also known as Radix bupleuri), has immunoregulatory, neuromodulatory, antiviral, anticancer, anti-convulsant, anti-inflammatory, and anti-proliferative effects. Recently, modulation of bone homeostasis was shown to involve ferroptosis. Herein, we aimed to determine Ssa's inhibitory effects on osteoclastogenesis and differentiation, whether ferroptosis is involved, and the underlying mechanisms. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit formation assays were conducted to confirm Ssa-mediated inhibition of RANKL-induced osteoclastogenesis in vitro. Ssa could promote osteoclast ferroptosis and increase mitochondrial damage by promoting lipid peroxidation, as measured by iron quantification, FerroOrange staining, Dichloro-dihydro-fluorescein diacetate, MitoSOX, malondialdehyde, glutathione, and boron-dipyrromethene 581/591 C11 assays. Pathway analysis showed that Ssa can promote osteoclasts ferroptosis by inhibiting the Nrf2/SCL7A11/GPX4 axis. Notably, we found that the ferroptosis inhibitor ferrostatin-1 and the Nrf2 activator tert-Butylhydroquinone reversed the inhibitory effects of Ssa on RANKL-induced osteoclastogenesis. In vivo, micro-computed tomography, hematoxylin and eosin staining, TRAP staining, enzyme-linked immunosorbent assays, and immunofluorescence confirmed that in rats with periodontitis induced by lipopolysaccharide, treatment with Ssa reduced alveolar bone resorption dose-dependently. The results suggested Ssa as a promising drug to treat osteolytic diseases.

Hepatocellular carcinoma is one of the common malignant tumors of digestive tract, which seriously threatens the life of patients due to its high incidence rate, strong invasion, metastasis, and prognosis. At present, the main methods for preventing and treating HCC include medication, surgery, and intervention, but patients frequently encounter with specific adverse reactions or side effects. Many Traditional Chinese medicine can improve liver function, reduce liver cancer recurrence and have unique advantages in the treatment of HCC because of their acting mode of multi-target, multi-pathway, multi-component, and multi-level. Sesquiterpenoids, a class of natural products which are widely present in nature and exhibit good anti-tumor activity, and many of them possess good potential for the treatment of HCC. This article reviewed the anti-tumor activities, natural resources, pharmacological mechanism of natural sesquiterpenoids against HCC, providing the theoretical basis for the prevention and treatment of HCC and a comprehensive understanding of their potential for development of new clinical drugs.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles published in or before June 2023 using PubMed, Google Scholar, and Web of Science. The searched keywords in scientific databases were ferroptosis, cancer, tumor, traditional Chinese medicine, botanical drugs, and phytomedicine. Only research related to ferroptosis, the metabolites from TCM, and cancer was considered. In this review, we introduce an overview of the current knowledge regarding the ferroptosis mechanisms and review the research advances on the metabolites of TCM inhibiting cancer by targeting ferroptosis.

Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth-inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit-8 assay after treatment with ART for 24 h, after which the half-maximal inhibitory concentration (IC50) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca2+) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl-xl, (myeloid cell leukaemia 1) Mcl-1, Bcl2-like protein 11 (BIM), (Bcl2-related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription-quantitative PCR. ART inhibited the growth of SiHa cells in a dose-dependent manner. The IC50 of ART in SiHa cells was 26.32 µg/ml. According to the IC50 value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca2+ and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl-xl and Mcl-1 in a dose- and time-dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca2+ and the reduction of the mitochondrial membrane potential.