Oxidative stress and endoplasmic reticulum stress contribute to subsp. M5L exopolysaccharide-induced apoptosis in HT-29 cells.

Colorectal cancer is the third most malignant cancer occurring around the world. Effective prevention and treatment have been increasingly the focus of global attention. Long-term diet of fermented dairy inhibits proliferation of colon cancer cell, which is considered that not only live lactic acid bacteria but also the secreted exopolysaccharides exert the function. In this scenario, this study aimed to investigate the mechanism of growth inhibition on HT-29 cells induced in vitro by exopolysaccharides isolated from subsp. M5L (M5-EPSs). HT-29 cells which were treated by a set of concentrations of M5-EPSs have been investigated of cell viability, characteristic changes, cell cycle distribution, and redox system. The results demonstrated that M5-EPSs treatments induced HT-29 cell apoptosis and resulted in upregulation of ROS levels and downregulation of antioxidant enzyme activities, leading to an imbalance in the oxidation system in HT-29 cells. In response to M5-EPSs, endogenous ER stress (ERS) markers, including GRP78, ATF4, and CHOP, were transcriptionally altered so that activating the ERS in HT-29 cells. After NAC treatment, the oxidative stress was inhibited, and the expression of GRP78 and CHOP was significantly decreased, indicating that oxidative stress can significantly affect the ERS pathway. Furthermore, it suggested that the occurrence of apoptosis was associated with Bcl-2 gene family. In conclusion, this study demonstrated that M5-EPSs can induce HT-29 cells apoptosis by destroying the redox system through activation of the ERS signaling pathway.