The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition.
A wealth of data implicates that ErbB receptors have essential roles in tumor development. Probiotic bacteria are known to exert an anticancer activity in animal studies. Bacillus polyfermenticus (B.P.), a probiotic bacterium, has been clinically used for a variety of gastrointestinal disorders in East Asia. Here, we investigated the effect of B.P. on the growth of tumors and its putative mechanism of actions. Conditioned medium of B.P. cultures (B.P. CM) inhibited the growth of human colon cancer cells including HT-29, DLD-1 and Caco-2 cells. Moreover, B.P. CM suppressed colony formation of HT-29 cells cultured on soft agar and reduced carcinogen-induced colony formation of normal colonocytes. Furthermore, data from the mouse xenograft model of human colon cancer cells showed reduced tumor size in B.P. CM-injected mice when compared to E. coli conditioned medium-injected mice. Exposure of B.P. CM to HT-29 cells for 24 hr, 48 hr and 2 weeks reduced ErbB2 and ErbB3 protein expression as well as mRNA levels. Moreover, cyclin D1 expression that is required for ErbB-dependent cell transformation was decreased by B.P. CM. Furthermore, transcription factor E2F-1 that regulates cyclin D1 expression was also decreased by B.P. CM. These results show that B.P. inhibits tumor growth and its anticancer activity occurs, at least in part, through suppressing ErbB2 and ErbB3. Taken together, our study suggests that this probiotic may be clinically used as a prophylactic treatment to prevent colon cancer development.
Ma
Elise L
EL
Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Choi
Yoon Jeong
YJ
Choi
Jinyoung
J
Pothoulakis
Charalabos
C
Rhee
Sang Hoon
SH
Im
Eunok
E
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001407:Bacillus / Q000502:physiology*; D015153:Blotting, Western; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3