The Cytotoxic Effect of Apis mellifera Venom with a Synergistic Potential of Its Two Main Components—Melittin and PLA2—On Colon Cancer HCT116 Cell Lines

Abstract

Colon carcinogenesis is ranked second globally among human diseases after cardiovascular failures. Bee venom (BV) has been shown to possess in vitro anticancer effects against several types of cancer cells. The two main biopeptides of Apis mellifera BV, namely, melittin (MEL) and phospholipase A2 (PLA2), are suspected to be the biomolecules responsible for the anticancer activity. The present work aims to evaluate the cytotoxic effect of the A. mellifera venom on human colon carcinoma cells (HCT116), and to assess the synergistic effect of MEL and PLA2 on these cells. After analyzing, through high-pressure liquid chromatography, the proportions of MEL and PLA2 on BV, we have established a cell viability assay to evaluate the effect of BV, MEL, PLA2, and a mixture of MEL and PLA2 on the HCT116 cells. Results obtained showed a strong cytotoxicity effect induced by the A. mellifera venom and to a lower extent MEL or PLA2 alone. Remarkably, when MEL and PLA2 were added together, their cytotoxic effect was greatly improved, suggesting a synergistic activity on HCT116 cells. These findings confirm the cytotoxic effect of the A. mellifera venom and highlight the presence of synergistic potential activities between MEL and PLA2, possibly inducing membrane disruption of HCT116 cancer cells. Altogether, these results could serve as a basis for the development of new anticancer treatments.

Apis mellifera syriaca Venom: Evaluation of Its Anticoagulant Effect, Proteolytic Activity, and Cytotoxicity along with Its Two Main Compounds—MEL and PLA2—On HeLa Cancer Cells

“…Altogether, these findings confirm the cytotoxic effect of A. mellifera syriaca venom on HeLa cancer cells in vitro. Additionally, the results support the hypothesis of our previous work, which suggests the importance of MEL in conferring the BV’s anticancer properties [ 23 ]. Moreover, by comparing the EC 50 values of BV, MEL, and Bv-PLA2 with those of our previous work on human colon cancer cells [ 23 ], we found that MEL is more effective on human colon cancer cells (EC 50 = 14.05 µg/mL) than on HeLa cells (EC 50 = 19.7 µg/mL).…”

“…Additionally, the results support the hypothesis of our previous work, which suggests the importance of MEL in conferring the BV’s anticancer properties [ 23 ]. Moreover, by comparing the EC 50 values of BV, MEL, and Bv-PLA2 with those of our previous work on human colon cancer cells [ 23 ], we found that MEL is more effective on human colon cancer cells (EC 50 = 14.05 µg/mL) than on HeLa cells (EC 50 = 19.7 µg/mL). In contrast, BV and Bv-PLA2 did not show a significant difference between the two types of cancer cells.…”

“…After demonstrating the cytotoxic effect of A. mellifera syriaca venom on HCT116 cells in our previous work [ 23 ], we aimed to expand our research by testing the effect of the same venom on different cancer cell lines. Accordingly, four concentrations of A. mellifera syriaca venom were tested on HeLa cancer cells.…”

“…Bee venom-phospholipase A2 (Bv-PLA2), a hydrolytic enzyme, belongs to the group III sPLA2 enzymes [ 14 ]; it is considered to be the most toxic enzyme in BV, and accounts for 12–15% of the crude BV’s dry weight [ 21 ]. Studies have shown that the activity of BV-PLA2 can be induced by MEL during the erythrocyte lysis process as well as the cytotoxic activity against cancer cells, proving the existence of a synergistic action between the two biomolecules [ 22 , 23 ]. Furthermore, the synergistic action between MEL and Bv-PLA2 was also demonstrated in a recent study, where the combination of Bv-PLA2 with MEL improved the inhibition extent of membrane-bound Escherichia coli F1F0-ATPAse [ 15 ].…”

“…Moreover, it has been shown that A. mellifera syriaca venom possesses a strong dose-dependent blocking effect on Escherichia coli F 1 F 0 -ATPase (with an IC 50 % higher than that obtained with the reference inhibitor of this enzyme) [ 15 ]. Furthermore, the venom has shown a considerable cytotoxic effect on different cancer cell lines, such as MCF-7 and HCT116 cell lines [ 4 , 23 ]. In this work, we evaluate for the first time the effects of A. mellifera syriaca venom on blood coagulation, as well as its proteolytic activity.…”