Song Wei, Hu Panpan, Guo Shouli, Hu Jinhong, Song Chen, Wang Tianyi, Gao Zihan, Yue Tianli
College of Food Science and Technology Northwest University Xi'an China.
Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering Xi'an China.
Food Sci Nutr. 2021 Jan 29;9(3):1676-1687. doi: 10.1002/fsn3.2142. eCollection 2021 Mar.
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.
结直肠癌是全球第三大恶性肿瘤。有效的预防和治疗日益成为全球关注的焦点。长期食用发酵乳制品可抑制结肠癌细胞的增殖，这被认为不仅是活的乳酸菌，而且其分泌的胞外多糖也发挥了作用。在这种情况下，本研究旨在探讨从亚种M5L分离的胞外多糖（M5-EPSs）体外诱导对HT-29细胞生长抑制的机制。研究了用一系列浓度的M5-EPSs处理的HT-29细胞的细胞活力、特征变化、细胞周期分布和氧化还原系统。结果表明，M5-EPSs处理诱导HT-29细胞凋亡，并导致ROS水平上调和抗氧化酶活性下调，导致HT-29细胞氧化系统失衡。响应M5-EPSs，包括GRP78、ATF4和CHOP在内的内源性内质网应激（ERS）标志物在转录水平上发生改变，从而激活HT-29细胞中的ERS。NAC处理后，氧化应激受到抑制，GRP78和CHOP的表达显著降低，表明氧化应激可显著影响ERS途径。此外，提示细胞凋亡的发生与Bcl-2基因家族有关。总之，本研究表明，M5-EPSs可通过激活ERS信号通路破坏氧化还原系统，诱导HT-29细胞凋亡。
