Cell-bound exopolysaccharide from probiotic bacteria induces autophagic cell death of tumour cells.
OBJECTIVE
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.


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.


CONCLUSIONS
These results may contribute to understanding the novel mechanisms by which probiotic bacteria induce tumour cell death via autophagy.
Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Kim
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Yun
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D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D015151:Immunoblotting; D007779:Lactobacillus acidophilus / Q000737:chemistry*; D008565:Membrane Proteins / Q000096:biosynthesis; D011135:Polysaccharides, Bacterial / Q000302:isolation & purification / Q000494:pharmacology*; D019936:Probiotics / Q000737:chemistry*; D020543:Proteome / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D011135:Polysaccharides, Bacterial; D020543:Proteome; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein