Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2025; 17(4): 104922
Published online Apr 15, 2025. doi: 10.4251/wjgo.v17.i4.104922
Tetramethylpyrazine induces reactive oxygen species-based mitochondria-mediated apoptosis in colon cancer cells
Yan-Xu Hou, Wei Ren, Qing-Qiang He, Li-Yan Huang, Tian-Hua Gao, Hua Li
Yan-Xu Hou, Wei Ren, Qing-Qiang He, Li-Yan Huang, Tian-Hua Gao, Hua Li, The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
Co-first authors: Yan-Xu Hou and Wei Ren.
Author contributions: Hou YX and Ren W contributed equally to this work; Li H designed the research; Ren W analyzed the data and drafted the manuscript; Hou YX revised the manuscript critically for important intellectual content and contributed to the data analysis; He QQ, Huang LY, and Gao TH helped draft the manuscript.
Institutional review board statement: The study was reviewed and approved by the Research Ethics Committee of Xingtai People’s Hospital.
Institutional animal care and use committee statement: Animal experiments were approved by the Research Ethics Committee of Xingtai People’s Hospital.
Conflict-of-interest statement: The authors declare no conflict of interest related to this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hua Li, PhD, Chief Physician, The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, No. 818 Xiangdu North Street, Xingtai 054001, Hebei Province, China. 19131344440@163.com
Received: January 8, 2025
Revised: January 26, 2025
Accepted: February 21, 2025
Published online: April 15, 2025
Processing time: 76 Days and 8.7 Hours
Abstract
BACKGROUND

Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. Chemotherapy resistance is the main cause of recurrence and progression in colon cancer. Thus, novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors.

AIM

To investigate the potential anticancer activity of TMP in colon cancer and the underlying mechanisms.

METHODS

Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay, and cell apoptosis was assessed by flow cytometry. Apoptosis-associated protein expression was measured using Western blot analysis. Intracellular reactive oxygen species (ROS) levels were assessed by flow cytometry using DCF fluorescence intensity. Xenografts were established by the subcutaneous injection of colon cancer cells into nude mice; tumor growth was monitored and intracellular ROS was detected in tumors by malondialdehyde assay.

RESULTS

TMP induced apoptosis of colon cancer cells via the activation of the mitochondrial pathway. TMP increased the generation of intracellular ROS and triggered mitochondria-mediated apoptosis in a caspase-dependent manner.

CONCLUSION

Our study demonstrates that TMP induces the apoptosis of colon cancer cells and increases the generation of intracellular ROS. TMP triggers mitochondria-mediated apoptosis in a caspase-dependent manner. The accumulation of intracellular ROS is involved in TMP-induced apoptosis. Our findings suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer.

Keywords: Tetramethylpyrazine; Colon cancer; Reactive oxygen species; Apoptosis; Cell proliferation

Core Tip: The incidence and mortality of colon cancer are increasing each year. Because of limited therapeutic treatments and low survival rate of advanced stage patients and the development of drug resistance, new treatments are urgently required. We found that tetramethylpyrazine (TMP) increases the generation of intracellular reactive oxygen species and triggers mitochondria-mediated apoptosis in a caspase-dependent manner. Our results suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer.