Dual Cytotoxic Responses Induced by Treatment of A549 Human Lung Cancer Cells with Sweet Bee Venom in a Dose-Dependent Manner

Abstract

Objectives: Sweet bee venom (sBV) is purified from Apis mellifera, containing a high level of melittin-its main component. It has been used as a therapeutic agent for pain relief and anti-inflammation, as well as for treating neuronal abnormalities. Recently, there have been studies on the therapeutic application of sBV for anticancer treatment. In the present study, we investigated the pharmacological effect of sBV treatment in A549 human lung cancer cells. Methods: We used microscopic analysis to observe the morphological changes in A549 cells after sBV treatment. The MTT assay was used to examine the cytotoxic effect after dose-dependent sBV treatment. Molecular changes in sBV were evaluated by the expression of apoptosis marker proteins using western blot analysis. Results: Microscopic analysis suggested that the growth inhibitory effect occurred in a dose-dependent manner; however, cell lysis occurred at a concentration over 20 µg/mL of sBV. The MTT assay indicated that sBV treatment exhibited a growth inhibitory effect at a concentration over 5 µg/mL. On fluorescence activated cell sorting analysis, G0 dead cells were observed after G1 arrest at treatment concentrations up to 10 µg/mL. However, rapid cell rupture was observed at a concentration of 20 µg/mL. Western blot analysis demonstrated that sBV treatment modulated the expression of multiple cell death-related proteins, including cleaved-PARP, cleaved-caspase 9, p53, Bcl2, and Bax. Conclusion: sBV induced cell death in A549 human lung cancer cells at a pharmacological concentration, albeit causing hemolytic cell death at a high concentration.