Cell‐bound exopolysaccharide from probiotic bacteria induces autophagic cell death of tumour cells

Aim: Lactic acid bacteria (LAB) are beneficial micro‐organisms that have been associated with several probiotic effects in both humans and animals. Here, using proteome analysis, we investigate the antitumour effects of cell‐bound exopolysaccharides (cb‐EPS) isolated from Lactobacillus acidophilus 606 on colon cancer cells and explore the proteins critical for their antitumour activity. Methods and Results: cb‐EPS inhibited the proliferation of HT‐29 colon cancer cells by directly affecting cell morphology and not the cell cycle. Using two‐dimensional polyacrylamide gel electrophoresis coupled with matrix‐assisted laser desorption‐ionization time‐of‐flight mass spectrometry (MALDI‐TOF/MS) and immunoblot analysis, we found that cb‐EPS dramatically induced Beclin‐1 and GRP78, and affected Bcl‐2 and Bak regulation. Conclusions: The results of this study indicate that cb‐EPS are antitumourigenic against HT‐29 colon cancer cells and that this activity is because of the activation of autophagic cell death promoted directly by the induction of Beclin‐1 and GRP78, as well as indirectly through the induction of Bcl‐2 and Bak. Significance and Impact of the Study: These results may contribute to understanding the novel mechanisms by which probiotic bacteria induce tumour cell death via autophagy.