N. Karem, A. Fahmy
Abstract: Breast cancer is the second leading cause of cancer death in women, on the other hand prostate cancer is the third leading cause of death in men worldwide. They are considered to be the most aggressive cancers due to failure in response to chemotherapy. Thus, there is an urgent need of finding alternative therapies for breast and prostate cancer. In present study, the anti-cancer properties and cytotoxicity of Lapatinab and bee venom on breast MCF-7 and prostate PC-3 cancer cell lines were evaluated using MTT assay and it was noticed that the cytotoxicity was concentration dependent recording IC50 of 60 g and 81 g and 288 M and 345 M for MCF-7 and PC-3 respectively. Furthermore, synergetic activity of both bee venom and Lapatinab to the other recording a significant decreased IC50 values in the order of 1.04 g and 0.59 g for BV and 178 M and 234 M for Lapatinab post MCF-7 and PC-3 respectively. The cell cycle arrest profile and specific cellular apoptosis markers were monitored (MMP1, CDK2, HER2, and P53) in bee venom and Lapatinab IC50 values pretreated MCF-7 and PC-3 cells using real time PCR and flow cytometric analysis. By analyzing the cell cycle arrest and related gene expression pattern, it was noticed that the main phase of cell cycle arrest was found to be G0/G1 in MCF-7 cell line. And S-phase arrest was also observed in bee venom pretreated breastMCF-7 cell line to a greater extent than that observed in cells only treated with Lapatinab. Up regulation of pro-apoptotic and down regulation of anti-apoptotic genes in bee venom pretreated cells were significantly enhanced as compared to cells treated with Lapatinab. In this study, we suggest that Lapatinab via its synergistic action with bee venom might be used as an enhancer of the anticancer properties of Lapatinab.
Keywords: Bee venom, Lapatinab, apoptosis, MCf-7 and PC-3 cell lines, Cell cycle, cytotoxicity, anticancer activity, MMP1, CDK7, HER2, P53