Scorpion Venom Peptide Effects on Inhibiting Proliferation and Inducing Apoptosis in Canine Mammary Gland Tumor Cell Lines

SIMPLE SUMMARY: Canine mammary gland tumors (CMGTs) are quite common in intact female dogs. In diagnosed cases, approximately 50% of mammary gland tumors metastasized. Chemotherapy is a practical treatment to increase the median survival time, but it has severe side effects and impacts on resistance. BmKn-2, an antimicrobial peptide derived from scorpion venom, has displayed anticancer effects in oral and colon human cancer cell lines. Consequently, BmKn-2 may be useful in the molecular treatment of CMGTs. This study investigated the effect of BmKn-2 on the proliferation inhibition, apoptotic induction and the related mechanisms of those actions in CMGT cell lines, metastatic (CHMp-5b) and non-metastatic (CHMp-13a). The experimental results showed that BmKn-2 effectively inhibited proliferation and induced apoptosis in both CMGT cell lines via Bcl-2 (B-cell lymphoma-2) down-regulation and Bax (Bcl2 associated X) up-regulation gene expressions. Therefore, BmKn-2 could be used as a candidate molecular treatment for CMGTs in the future. ABSTRACT: The most common neoplasms in intact female dogs are CMGTs. BmKn-2, an antimicrobial peptide, is derived from scorpion venom and has published anticancer effects in oral and colon human cancer cell lines. Thus, it is highly likely that BmKn-2 could inhibit CMGT cell lines which has not been previously reported. This study investigated the proliferation and apoptotic properties of BmKn-2 via Bax and Bcl-2 relative gene expression in two CMGT cell lines, metastatic (CHMp-5b) and non-metastatic (CHMp-13a). The results showed that BmKn-2 inhibited proliferation and induced apoptosis in the CMGT cell lines. The cell morphology clearly changed and increased apoptosis in a dose dependent of manner. The half maximum inhibitory concentration (IC(50)) was 30 µg/mL for CHMp-5b cell line and 54 µg/mL for CHMp-13a cell line. The induction of apoptosis was mediated through Bcl-2 and Bax expression after BmKn-2 treatment. In conclusion, BmKn-2 inhibited proliferation and induced apoptosis in both CHMp-5b and CHMp-13a cell lines via down-regulation of Bcl-2 and up-regulation of Bax relative mRNA expression. Therefore, BmKn-2 could be feasible as candidate treatment for CMGTs.