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.