The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition

Abstract

A wealth of data implicates that ErbB receptors have essential roles in tumor development. Probiotic bacteria are known to exert an anti-cancer 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 h, 48 h and 2 weeks reduced ErbB2 and ErbB3 protein expression as well as mRNA levels. Moreover, cyclin D1 expression which is required for ErbB-dependent cell transformation was decreased by B.P. CM. Furthermore, transcription factor E2F-1 which regulates cyclin D1 expression was also decreased by B.P. CM. These results show that B.P. inhibits tumor growth and its anti-cancer 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.

Screening and In-Vitro Analysis of Lactobacillus reuteri Strains for Short Chain Fatty Acids Production, Stability and Therapeutic Potentials in Colorectal Cancer

“…3), respectively, compared to untreated cells. These observations, shown for the first time, are consistent with the findings that LAB and, more specifically, L. reuteri, may have anticancer activity induced by SCFA production in the colon which may decrease tumor growth, inhibit colon cancer cell growth, and promote apoptosis [39]. It is possible that probiotic bacteria have altered colon cancer cell metabolism.…”

Cancer and the microbiome: potential applications as new tumor biomarker

“…In contrast, certain organisms of the microbiome may contribute to reduce the incidence of cancer. A probiotic bacterium, Bacillus polyfermenticus, has been shown to impair the growth of human colon cancer cells by the inhibition of ErbB2 and ErbB3 receptors [104]. The specific mechanisms behind the association between bacteria and cancer development include immune evasion, chronic inflammation and immune suppression [36,105].…”

Hypothesis: Bacteria Control Host Appetites

“…Media conditioned by the growth of Bacillus polyfermenticus inhibited the growth of human colon cancer cells in vitro and of tumors of such cells in mouse xenograft experiments (39); these effects were associated with a reduction in the mRNA and protein levels of ErbB2 and ErbB3 as well as the levels of E2F-1, which regulates CyclinD1 production, and of CyclinD1 itself, which is required for ErbB-dependent transformation These results have led to B. polyfermenticus administration being proposed as a preventative treatment for bowel cancer (39). Recently, inflammation was shown to increase the frequency of colorectal cancer in mice by favoring the proliferation of an E. coli strain that produces a DNA-damaging toxin, colibactin (40).…”