Comprehensive evaluation of the anticancer activity of Egyptian bee venom (Apis mellifera): cytotoxic effects on diverse human cancer cell lines and tumor suppression in EAC mice
摘要
Bee venom (BV) contains a variety of bioactive agents, including peptides and enzymes, which possess anti-inflammatory, antioxidant, and antitumor properties. The current research aimed to investigate the in vitro cytotoxic effects of BV against human breast ductal carcinoma (T-47D), resistant T-47D, human pancreatic cancer (Panc-1), human prostate cancer (Pc-3), and human normal breast cell (MCF-10A) proliferation by using the MTT assay. The study also extended to evaluate the antitumor effect of bee venom on the Ehrlich solid tumor in vivo.
ResultsTreatment with BV demonstrated a notable dose-dependent anticancer effect, particularly on T-47D, resistant T-47D, PC-3, PANC-1, and normal MCF-10A cells after 24 h, with IC50 values ranging between 1.3 and 5.8 μg/mL whereas the most sensitive cell lines are breast cancer cell lines, T-47D, and the resistant T-47D with selective indices of 55.59 and 39.98, respectively; therefore, these cells were chosen for further analysis. SDS-PAGE of BV revealed the presence of proteins between 10 and ~ 44 kDa. Flow cytometry analysis presented that BV induced G1-phase T-47D cell arrest. In T-47D cells, BV also resulted in a much higher rate of DNA fragmentation. Furthermore, Annexin V-FITC/PI double staining illustrated the mechanism of the cytotoxic properties of BV in T-47D and resistant cells through apoptosis, which was confirmed with increased expression of pro-apoptotic protein (BAX) and reduced levels of the anti-apoptotic (Bcl-2) protein, as shown immunohistochemically in vivo. An in vivo study demonstrated that BV significantly reduced the Ehrlich solid tumor weight and volume with minimal toxicity.
ConclusionBee venom is a promising natural agent with potent in vitro and in vivo activity against both cancer and resistant cancer cells, showing potential for synergistic use with conventional chemotherapy.