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.
Kim
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Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Yun
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Kim
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SH
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