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

Wei Song; Panpan Hu; Shouli Guo; Jinhong Hu; Chen Song; Tianyi Wang; Zihan Gao; Tianli Yue

doi:10.1002/fsn3.2142

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

Food Sci Nutr. 2021 Jan 29;9(3):1676-1687. doi: 10.1002/fsn3.2142. eCollection 2021 Mar.

Authors

Wei Song^{1

2

3}, Panpan Hu⁴, Shouli Guo⁵, Jinhong Hu^{1

2

3}, Chen Song^{6

7}, Tianyi Wang^{6

7}, Zihan Gao^{1

2

3}, Tianli Yue^{1

2

3}

Affiliations

¹ College of Food Science and Technology Northwest University Xi'an China.
² Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering Xi'an China.
³ Research Center of Food Safety Risk Assessment and Control Xi'an China.
⁴ Department of Life Science Luliang University Lv Liang China.
⁵ Animal Experiment Center of the Second Affiliated Hospital Harbin Medical University Harbin China.
⁶ College of Chemical Engineering and Chemistry Harbin Institute of Technology Harbin China.
⁷ National Local Joint Laboratory of Extreme Environmental Nutritional Molecule Synthesis Transformation and Separation Harbin China.

Abstract

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 Lactobacillus paracasei subsp. paracasei 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.

Keywords: HT‐29 cells; M5‐EPSs; apoptosis; endoplasmic reticulum stress; oxidative stress.