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Bee Venom and Melittin from Apis Mellifera Display Cytotoxicity towards Different Types of Tumor and Non-tumor Cell Lines

Bee venom is used in traditional medicine to treat variety of diseases. In recent years it has also been reported that the venom and, especially one of its major constituent’s melittin, possess anticancer properties. The aim of this chapter was to evaluate the cytotoxicity of whole bee venom, and melittin towards different types of tumor cells: human laryngeal HEp-2 and cervical carcinoma HeLa cells and their drug resistant sublines (CK2 and HeLa CK cells), breast adenocarcinoma MCF-7 cells, colon adenocarcinoma SW620 cells, and glioblastoma A1235 cells, as well as human embryonic kidney HEK-293 cells and normal Hef fibroblasts. Bee venom was tested in concentrations ranging from 0.4 μg/ml to 200 μg/ml, and melittin in concentrations from 0.1 μg/ml to 50 μg/ml. Cytotoxicity of whole bee venom, and melittin was evaluated using spectrophotometric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test. The morphology of treated cells was determined by light and fluorescent microscopy. Our results show that both, bee venom and melittin have strong cytotoxic potential towards different human cultured tumor cells, and that their effects are dose and cell type dependent. Melittin displayed even greater cytotoxicity to all types of cells tested. In addition, tumor cells were more sensitive to both, bee venom and melittin, as compared to the non-tumor cells. Depending on the origin, drug-resistant cells could be more sensitive to melittin (such as drug resistant cervical carcinoma cells) than parental cells. Both, bee venom and melittin altered morphological characteristics of treated cells. They were induced rapidly, in less than one hour following the treatment with bee venom or melittin. Light microscopy showed that bee venom and melittin treated cells exhibited significant morphological changes in addition to the cell viability reduction. Morphological features were rounded and granulated morphology, cell shrinkage and eventual detachment from the culture plates. Their fast staining with ethidium bromide suggests that both, bee venom and melittin given in higher doses induced probably necrotic type of cell death. Our further studies will focus on the mechanisms by which bee venom itself and its components lead to cell death. Our data in conjunction with other accumulating evidence on anti-proliferative and pro-death activity of bee venom and melittin indicate their possible use in the development of antitumor drugs.

Bee venom, Melittin, Cytotoxicity, Tumor cells, Non-tumor cells, Cell death

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