• cell death
• ddc
• fibrosis
• p21
• rock

• Animals
• rho-Associated Kinases/metabolism
• rho-Associated Kinases/genetics
• Hepatocytes/metabolism
• Hepatocytes/pathology
• Mice
• Signal Transduction
• Mice, Knockout
• Apoptosis
• Disease Models, Animal
• Male
• Pyridines/pharmacology
• Liver/pathology
• Chemical and Drug Induced Liver Injury/genetics
• Chemical and Drug Induced Liver Injury/pathology

• P30 DK026743 NIDDK NIH HHS

• apoptosis
• cartilage development

• Caspases/metabolism
• Cathepsin D/metabolism
• Apoptosis/physiology
• Cellular Senescence/physiology
• Lysosomes/metabolism

• Predoctoral Universidad de Cantabria (University of Cantabria)
• Spanish Science and Innovation Ministry Grant (PID2021-12665NB-100)

• Humans
• Apoptosis
• beta-Thalassemia/genetics
• Cyclin-Dependent Kinase Inhibitor p21/genetics
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• Erythropoiesis/genetics
• Splenomegaly

• R01 HL061567 NHLBI NIH HHS
• T32 HD075735 NICHD NIH HHS
• R01 DK090554 NIDDK NIH HHS
• R01 HL161567 NHLBI NIH HHS
• R01 DK095112 NIDDK NIH HHS
• R01 CA205975 NCI NIH HHS
• R01 HL136255 NHLBI NIH HHS

• Deoxyribonucleic acid
• Fluorescence
• Molecular dynamics
• Nuclear magnetic resonance spectroscopy
• Resveratrol

• Base Sequence
• Binding Sites
• Magnetic Resonance Spectroscopy
• Molecular Dynamics Simulation
• Nucleic Acid Conformation
• Promoter Regions, Genetic
• Resveratrol
• Sequence Analysis, DNA

• Cell cycle
• DNA synthesis
• Ellagic acid
• Gene expression
• RNA-seq

Human lymphocytes exposed to Aggregatibacter actinomycetemcomitans (Aa) cytolethal distending toxin (Cdt) undergo cell cycle arrest and apoptosis. In previous studies, we demonstrated that the active Cdt subunit, CdtB, is a potent phosphatidylinositol (PI) 3,4,5-triphosphate phosphatase. Moreover, AaCdt-treated cells exhibit evidence of PI-3-kinase (PI-3K) signaling blockade characterized by reduced levels of PIP3, pAkt, and pGSK3β. We have also demonstrated that PI-3K blockade is a requisite of AaCdt-induced toxicity in lymphocytes. In this study, we extended our observations to include assessment of Cdts from Haemophilus ducreyi (HdCdt) and Campylobacter jejuni (CjCdt). We now report that the CdtB subunit from HdCdt and CjCdt, similar to that of AaCdt, exhibit potent PIP3 phosphatase activity and that Jurkat cells treated with these Cdts exhibit PI-3K signaling blockade: reduced levels of pAkt and pGSK3β. Since non-phosphorylated GSK3β is the active form of this kinase, we compared Cdts for dependence on GSK3β activity. Two GSK3β inhibitors were employed, LY2090314 and CHIR99021; both inhibitors blocked the ability of Cdts to induce cell cycle arrest. We have previously demonstrated that AaCdt induces increases in the CDK inhibitor, p21^CIP1/WAF1, and, further, that this was a requisite for toxin-induced cell death via apoptosis. We now demonstrate that HdCdt and CjCdt also share this requirement. It is also noteworthy that p21^CIP1/WAF1 was not involved in the ability of the three Cdts to induce cell cycle arrest. Finally, we demonstrate that, like AaCdt, HdCdt is dependent upon the host cell protein, cellugyrin, for its toxicity (and presumably internalization of CdtB); CjCdt was not dependent upon this protein. The implications of these findings as they relate to Cdt’s molecular mode of action are discussed.

• apoptosis
• cell cycle arrest
• cytolethal distending toxin
• host-parasite interactions
• lymphocytes
• pathogenesis
• toxins

• Apoptosis
• Cancer radiotherapy
• Cell cycle
• DNA damage repair
• p21

• Animals
• Cellular Senescence
• Cyclin-Dependent Kinase Inhibitor p21/genetics
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/radiotherapy
• Radiation, Ionizing
• Signal Transduction

• Motor neuron
• Mouse
• Smn(2B/−)
• Spinal muscular atrophy (SMA)
• Survival motor neuron (SMN)
• p21 (cdkn1a)
• p53

• DNMT1
• G0/G1 cell cycle arrest
• oral squamous cell carcinoma
• p21
• statins

• TCMRC-P-108003 Tzu Chi University

Cisplatin-based therapy is a widely used chemotherapeutic regimen for non-small cell lung cancer (NSCLC); however, drug resistance limits its efficacy. Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive compound from frankincense, has been shown to exert anti-cancer effects. The aim of this study is to explore the potential of AKBA in combination with cisplatin as a new regimen for NSCLC. CCK8 assay and clone formation assay were used to determine the effects of AKBA in combination with cisplatin on cell viability of NSCLC cell lines. A three-dimensional spherification assay was used to simulate in vivo tumor formation. Flow cytometry was performed to examine cell cycle distribution and the percentages of apoptotic cells. The associated proteins and mRNA of cell cycle, apoptosis, and autophagy were measured by western blotting and real-time fluorescence quantitative PCR. Immunofluorescence assay was used to test apoptotic nuclei and autolysosome. Small interfering RNA experiments were used to silence the expression of p21. Combination treatment of AKBA and cisplatin inhibited cell viability, clone formation, and three-dimensional spherification, enhanced G₀/G₁ phase arrest, increased the percentages of apoptotic cells, and decreased the ratio of positive autolysosomes, compared with cisplatin alone. AKBA in combination with cisplatin suppressed the protein expressions of cyclin A2, cyclin E1, p-cdc2, CDK4, Bcl-xl, Atg5, and LC3A/B, and upregulated p27 and p21 mRNA levels in A549 cells. Downregulation of p21 decreased G₀/G₁ phase arrest and the percentages of apoptotic cells, and promoted autophagy in NSCLC A549 cells. Our study demonstrates that AKBA enhances the cisplatin sensitivity of NSCLC cells and that the mechanisms involve G₀/G₁ phase arrest, apoptosis induction, and autophagy suppression via targeting p21-dependent signaling pathway.

• Acetyl-11-keto-β-boswellic acid
• Apoptosis
• Autophagy
• Cell cycle
• Cisplatin
• Non-small cell lung cancer
• p21

The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) induces lymphocytes to undergo cell-cycle arrest and apoptosis; toxicity is dependent upon the active Cdt subunit, CdtB. We now demonstrate that p21^CIP1/WAF1 is critical to Cdt-induced apoptosis. Cdt induces increases in the levels of p21^CIP1/WAF1 in lymphoid cell lines, Jurkat and MyLa, and in primary human lymphocytes. These increases were dependent upon CdtB’s ability to function as a phosphatidylinositol (PI) 3,4,5-triphosphate (PIP3) phosphatase. It is noteworthy that Cdt-induced increases in the levels of p21^CIP1/WAF1 were accompanied by a significant decline in the levels of phosphorylated p21^CIP1/WAF1. The significance of Cdt-induced p21^CIP1/WAF1 increase was assessed by preventing these changes with a two-pronged approach; pre-incubation with the novel p21^CIP1/WAF1 inhibitor, UC2288, and development of a p21^CIP1/WAF1-deficient cell line (Jurkat^p21−) using clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 gene editing. UC2288 blocked toxin-induced increases in p21^CIP1/WAF1, and Jurkat^WT cells treated with this inhibitor exhibited reduced susceptibility to Cdt-induced apoptosis. Likewise, Jurkat^p21− cells failed to undergo toxin-induced apoptosis. The linkage between Cdt, p21^CIP1/WAF1, and apoptosis was further established by demonstrating that Cdt-induced increases in levels of the pro-apoptotic proteins Bid, Bax, and Bak were dependent upon p21^CIP1/WAF1 as these changes were not observed in Jurkat^p21− cells. Finally, we determined that the p21^CIP1/WAF1 increases were dependent upon toxin-induced increases in the level and activity of the chaperone heat shock protein (HSP) 90. We propose that p21^CIP1/WAF1 plays a key pro-apoptotic role in mediating Cdt-induced toxicity.

• Keywords Aggregatibacter actinomycetemcomitans
• apoptosis
• cytolethal distending toxin
• lymphocytes
• virulence

DNA damage and DNA damage response (DDR) pathways in β-cells have received little attention especially in the context of type-2 diabetes. We postulate that p21 plays a key role in DDR by preventing apoptosis, associated through its overexpression triggered by DNA stand breaks (DSBs). Our results show that β-cells from chronic diabetic mice had a greater extent of DSBs as compared to their non-diabetic counterparts. Comet assays and nuclear presence of γH2AX and 53bp1 revealed increased DNA DSBs in 16 weeks old (wo) db/db β-cells as compared to age matched non-diabetic β-cells. Our study of gene expression changes in MIN6 cell line with doxorubicin (Dox) induced DNA damage, showed that the DDR was similar to primary β-cells from diabetic mice. There was significant overexpression of DDR genes, gadd45a and p21 after a 24-hr treatment. Western blot analysis revealed increased cleaved caspase3 over time, suggesting higher frequency of apoptosis due to Dox-induced DNA strand breaks. Inhibition of p21 by pharmacological inhibitor UC2288 under DNA damage conditions (both in Dox-induced MIN6 cells and older db/db islets) significantly increased the incidence of β-cell apoptosis. Our studies confirmed that while DNA damage, specifically DSBs, induced p21 overexpression in β-cells and triggered the p53/p21 cellular response, p21 inhibition exacerbated the frequency of apoptosis.

• Genistein
• Pituitary
• Proliferation
• Senescence

• cancer therapy
• cell cycle
• chemoresistance
• dual role
• p21
• signaling pathways

Multiple myeloma (MM) is a hematological malignancy of plasma cells that produce a monoclonal immunoglobulin protein. Despite significant advances in the treatment of MM, challenges such as resistance to therapy remain. Currently, inhibition of histone deacetylases (HDACs) is emerging as a potential method for treating cancers. Numerous HDAC inhibitors are being studied for the use in monotherapy or in conjunction with other agents for MM. In the present study, we investigated the anti-myeloma effect of Nexturastat A (NexA), a novel selective HDAC6 inhibitor. We found that NexA impaired MM cells viability in a dose- and time-dependent manner. NexA also provoked a cell cycle arrest at the G1 phase in MM cells. Furthermore, NexA promoted apoptosis of MM cells via transcriptional activation of the p21 promoter, which may through its ability to up-regulate the H3Ac and H4Ac levels. Additionally, NexA could overcome bortezomib (BTZ) resistance in MM cells, and NexA in combination with BTZ had stronger efficacy. We also confirmed that NexA inhibited tumor growth in murine xenograft models of MM. These interesting findings provided the rationale for the future advancement of this novel HDAC6 inhibitor as a potential therapeutic anti-myeloma agent.

• Nexturastat A
• apoptosis
• drug resistance
• multiple myeloma
• p21

Molt-4 leukemia cells undergo p53-dependent apoptosis accompanied by accumulation of de novo ceramide after 14 hours of γ-irradiation. In order to identify the potential mediators involved in ceramide accumulation and the cell death response, differentially expressed genes were identified by Affymetrix Microarray Analysis. Molt-4-LXSN cells, expressing wild type p53, and p53-deficient Molt-4-E6 cells were irradiated and harvested at 3 and 8 hours post-irradiation. Human genome U133 plus 2.0 array containing >47,000 transcripts was used for gene expression profiling. From over 10,000 probes, 281 and 12 probes were differentially expressed in Molt-4-LXSN and Molt-4-E6 cells, respectively. Data analysis revealed 63 (upregulated) and 20 (downregulated) genes (>2 fold) in Molt-4-LXSN at 3 hours and 140 (upregulated) and 21 (downregulated) at 8 hours post-irradiation. In Molt-4-E6 cells, 5 (upregulated) genes each were found at 3 hours and 8 hours, respectively. In Molt-4-LXSN cells, a significant fraction of the genes with altered expression at 3 hours were found to be involved in apoptosis signaling pathway (BCL2L11), p53 pathway (PMAIP1, CDKN1A and FAS) and oxidative stress response (FDXR, CROT and JUN). Similarly, at 8 hours the genes with altered expression were involved in the apoptosis signaling pathway (BAX, BIK and JUN), p53 pathway (BAX, CDKN1A and FAS), oxidative stress response (FDXR and CROT) and p53 pathway feedback loops 2 (MDM2 and CDKN1A). A global molecular and biological interaction map analysis showed an association of these altered genes with apoptosis, senescence, DNA damage, oxidative stress, cell cycle arrest and caspase activation. In a targeted study, activation of apoptosis correlated with changes in gene expression of some of the above genes and revealed sequential activation of both intrinsic and extrinsic apoptotic pathways that precede ceramide accumulation and subsequent execution of apoptosis. One or more of these altered genes may be involved in p53-dependent ceramide accumulation.

Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis. In C4-2B cells the combination up regulated the expression of p53, and cell cycle inhibitors (p21^WAF1/CIP1, p27^KIP), which, in turn, inhibited the expression of CDK4, cyclin D1, cyclin E1 and induced hypo-phosphorylation of Rb thus blocking the transition of cells in the G₀/G₁ to S phase. In contrast, the synergistic effect was not profound in DU145 due to its lesser sensitivity to DTX. The suppression of cyclin B1 and CDK1 expression in both cell lines inhibits the further progression of cells in G₂/M phase. The current study demonstrates that combination treatment blocks the cell cycle arrest by modulation of key regulators and promotes apoptosis via p53 dependent and independent mechanism in PCa.

• cell cycle
• docetaxel
• p21
• p53
• resveratrol

• Anticancer activity
• Benzofurans
• Breast cancer
• p21Cip/WAF1

• Anticancer
• BrdU
• Free radicals
• G2/M arrest
• HPLC
• WI-38

As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells (IC₅₀ = 5 μM) and induced apoptosis. Here, we investigated the mechanism of action of EB in cancer cell lines of the prostate (LNCaP) and breast (MDA-MB-231). EB inhibited cell growth (IC₅₀ = 5 μM) and induced a G2 cell cycle arrest, as shown by a significant increase in the G2/M cell population in the absence of elevated levels of the mitotic marker phospho-histone H3. In contrast to MDA-MB-231 cells, EB did not induce cell death in LNCaP cells when treated for up to 10 days. Transcript profiling and Ingenuity Pathway Analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, CHK2 phosphorylation was increased, p21^CIP1/WAF1 was up-regulated and CDC2 expression strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison.

• DNA damage
• G2/M arrest
• LNCaP
• eusynstyelamide B
• topoisomerase II poison

Despite the large popularity of the Boletus edulis mushroom, little is known about its influence on human health and the possibilities of its therapeutic use.

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.

Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC₅₀ values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.

Prostate cancer has been extensively studied, but cellular stress responses in healthy prostate tissue are rarely investigated. Hypothermia is known to cause alterations in mRNA and protein expressions and stability. The aim of this study was to use normal rat prostate as a model in order to find out consequences of cold exposure and rewarming on the expressions of genes which are either members or functionally/structurally related to erythroblastic leukemia viral oncogene B (ErbB) signaling pathway. Relative mRNA expressions of amphiregulin (AMR), cyclin D1 (CyD1), cyclin-dependent kinase inhibitor 1A (p21), transmembrane form of the prostatic acid phosphatase (PAcP), thrombomodulin (TM) and heat shock transcription factor 1 (HSF1) in rat ventral prostate were quantified in mild (2 or 4.5 h at room temperature) and severe (2 or 4.5 h at +10°C) hypothermia and in rewarming after cold exposure (2 h at +10°C followed by 2 h at room temperature or 3 h at +28°C). AMR protein level, apoptotic Bcl-2 associated X protein to B-cell CLL/lymphoma 2 (Bax/Bcl-2) mRNA ratio and proliferative index Ki-67 were determined. 4.5-h mild hypothermia, 2-h severe hypothermia and rewarming increased expression of all these genes. Elevated proliferation index Ki-67 could be seen in 2-h severe hypothermia, and the proliferation index had its highest value in longer rewarming with totally recovered normal body temperature. Pro-apoptotic tendency could be seen in 2-h mild hypothermia while anti-apoptosis was predominant in 4.5-h mild hypothermia and in shorter rewarming with only partly recovered body temperature. Hypothermia and following rewarming promote the proliferation of cells in healthy rat prostate tissue possibly via ErbB signaling pathway.

• Amphiregulin/genetics
• Animals
• Gene Expression Regulation
• Genes, bcl-2
• Hypothermia
• Immunohistochemistry
• Male
• Prostate/metabolism
• RNA, Messenger/genetics
• Rats
• Rewarming
• bcl-2-Associated X Protein/genetics

• tgfβ/smad signaling
• tumor suppression
• cell cycle arrest
• apoptosis
• p21
• lif
• stat3
• melanoma
• cell migration

• Adult
• Apoptosis/genetics
• Cell Cycle Checkpoints/genetics
• Cell Movement/genetics
• Cell Proliferation/genetics
• Cyclin-Dependent Kinase Inhibitor p21/genetics
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Leukemia Inhibitory Factor/biosynthesis
• Leukemia Inhibitory Factor/genetics
• Male
• Melanoma/genetics
• Melanoma/metabolism
• Melanoma/pathology
• Middle Aged
• Primary Cell Culture
• Protein Binding
• STAT3 Transcription Factor/genetics
• Signal Transduction/genetics
• Skin Neoplasms/genetics
• Skin Neoplasms/metabolism
• Skin Neoplasms/pathology
• Transforming Growth Factor beta1/genetics
• Transforming Growth Factor beta1/metabolism
• Melanoma, Cutaneous Malignant

• Canadian Institutes of Health Research

• 5-FU
• Apoptosis
• Colorectal Cancer
• Drug Resistance
• MicroRNA (miRNA)
• miR-520g
• p21
• p53

• Anthracenes/radiation effects
• Anthracenes/toxicity
• Apoptosis
• Caspase 3/metabolism
• Cell Cycle/drug effects
• Cell Line
• Cyclin-Dependent Kinase Inhibitor p21/genetics
• DNA Damage
• Environmental Pollutants/radiation effects
• Environmental Pollutants/toxicity
• Gene Expression Regulation/drug effects
• Humans
• Linoleic Acid/chemistry
• Linoleic Acid/radiation effects
• Lysosomes/drug effects
• Lysosomes/metabolism
• Membrane Potential, Mitochondrial
• Mitochondria/drug effects
• Mitochondria/metabolism
• Phosphatidylserines/metabolism
• Proto-Oncogene Proteins c-bcl-2/genetics
• Reactive Oxygen Species/metabolism
• Singlet Oxygen/chemistry
• Ultraviolet Rays
• bcl-2-Associated X Protein/genetics

• ALDH1L1
• PUMA
• apoptosis
• cell cycle arrest
• folate metabolism
• p21

JKA97, a benzylidene analog of harmine, has been found to be a promising drug candidate for human cancer therapy, although the underlying molecular mechanisms have not been fully demonstrated. In this study, we evaluated the effects of JKA97 on human breast cancer cells in vitro and in vivo. JKA97 inhibited the growth and proliferation of MCF7 (p53 wild-type), MCF7 (p53 knockdown), and MDA-MB-468 (p53 mutant) cells in a dose-dependent manner. Treatment with JKA97 arrested breast cancer cells in G1 phase and induced apoptosis. JKA97 also significantly suppressed the growth of MCF7 and MDA-MB-468 xenograft tumors. It regulated the expression levels of G1 phase regulators, such as p21, p27, cyclinE, and cylinD1. JKA97 activated p21 transcription, independent of p53, but had little effect on p21 protein stability/degradation. In summary, our results suggest that JKA97 inhibits human breast cancer cell growth through activating p21, independent of p53, which provides a basis for developing this compound as a novel drug for human breast cancer therapy.

• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Benzylidene Compounds/chemistry
• Benzylidene Compounds/pharmacology
• Breast Neoplasms/drug therapy
• Breast Neoplasms/metabolism
• Carbolines/chemistry
• Carbolines/pharmacology
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• Dose-Response Relationship, Drug
• Female
• G1 Phase Cell Cycle Checkpoints/drug effects
• Gene Expression Regulation/drug effects
• Harmine/chemistry
• Humans
• In Vitro Techniques
• Styrenes/chemistry
• Styrenes/pharmacology

• R01 CA091980 NCI NIH HHS
• R15 CA100102 NCI NIH HHS
• R01 CA112029 NCI NIH HHS
• R01 CA121211 NCI NIH HHS
• BCTR070731 PHS HHS
• R01 CA91980 NCI NIH HHS

• Apoptosis/drug effects
• Cadherins/genetics
• Carcinoma, Non-Small-Cell Lung/diet therapy
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/pathology
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• DNA-Binding Proteins/genetics
• Down-Regulation/drug effects
• Down-Regulation/genetics
• Enhancer of Zeste Homolog 2 Protein
• Histone Deacetylases/genetics
• Humans
• Methotrexate/pharmacology
• Polycomb Repressive Complex 2
• Transcription Factors/genetics
• Tumor Suppressor Protein p53/metabolism

• Animals
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• Sphingolipids/metabolism

• P20 RR016456 NCRR NIH HHS
• P20 RR016456-03S2 NCRR NIH HHS
• P20 RR16456 NCRR NIH HHS

• musashi-1
• gamma irradiation
• survivin
• crypt survival