Antiproliferative Effect of Gallic Acid is Mediated via Mitochondrial- or ER-Stress-Induced Apoptosis and Canonical Autophagy in HT-29 Cells

Cancer is a noncommunicable disease burden and the second-leading cause of death worldwide. Novel medications and drug possibilities are sought everyday throughout the world in pursuit of cancer therapy. Colorectal cancer as one of the leading cancers across the globe can be treated effectively using TCM via decreasing the incidence and increasing the survival of patients. Gallic acid (GA) is an effective polyphenol used in TCM to treat several disorders including cancer. Our hypothesis was set to determine that GA possesses cytotoxic effects on CRC cells and that apoptosis and/or autophagy could be the rationale behind the mechanism. Therefore, in the current study, we investigated the cytotoxic effects of GA on human colorectal adenocarcinoma HT-29 cells and the mechanisms of such effects. The IC50 for the cytotoxic effects of GA as evidenced by the MTT assay was 37.08 μg/mL. The outcomes indicated that GA can cause changes in MMP and result in the formation or accumulation of exogenous ROS at the IC50 dose. Consequently, the polyphenol can induce mitochondrial- or ER-stress-induced apoptosis and canonical autophagy other than contributing to the induction of ferroptosis in HT-29 cells as evidenced by quantitative PCR and western blotting. Our results indicate that GA is an effective cytotoxic agent for the management of CRC at the preclinical level and is a valuable candidate for clinical trials.