Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice

Abstract

Abstract. The present study was designed to confirm whether the Bowman-Birk inhibitor (BBI) induces an increase in p27 accumulation without S phase kinase-associated protein 2 (skp2) degradation by means of the expression of connexin (Cx) 43 as a gap junctional intercellular communication (GJIC)-dependent pathway in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x10 5 cells/animal) were subcutaneously transplanted onto the backs of BDF 1 mice receiving 10, 20 or 40 mg/kg of purified BBI intraperitoneally. Relative tumor weight (p<0.01, r=0.503) was negatively correlated with the dose of BBI. In contrast, the relative density of Cx43 mRNA (p<0.01, r=0.570) and Cx43 (p<0.01, r=0.718) was positively correlated with the dose of BBI, as were p21 (p<0.01, r=0.633), p27 (p<0.01, r=0.561) and skp2 (p<0.01, r=0.733). We therefore suggest that the anticarcinogenic effects of BBI induce negative growth control by means of an increase in p27 accumulation caused by the expression of Cx43 as a GJIC pathway.

Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications

“…Notably, BBI did not affect Cx43 expression in non-tumorigenic cells. Similarly, BBI-induced expression of Cx43 has also been reported in mice with M5076 ovarian sarcoma [149,150], in human prostate cancer LNCaP cells, and in prostate adenocarcinomas in vivo model [147]. Besides soybean-derived BBI, another member of the family, the black-eyed pea derived BTCI, is able to inhibit proteasomal proteolytic activity.…”

“…M5076 sarcoma xenograft mouse model [149,150] Reduction of relative tumor weight associated with induced expression of Cx43.…”