Potentiation of Bleomycin Lethality in HeLa and V79 Cells by Bee Venom

Abstract

This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that some calcium antagonists and calmodulin inhibitors enhanced intracellular levels of antitumor agents by inhibiting their outward transport. In this study, treatment of exponentially growing HeLa and V79 cells with bleomycin caused a dose-dependent decrease in cell survival due to DNA damage. This lethal effect was potentiated by adding a non-lethal dose of the bee venom. By preventing repair of damaged DNA, bee venom inhibited recovery from potentially lethal damage induced by bleomycin in V79 and HeLa cells. Apoptosis, necrosis, and lysis were presumed as possible mechanisms by which bee venom inhibited growth and clonogenicity of V79 cells. HeLa cells, on the other hand, showed greater resistance to bee venom. Our fi ndings suggest that bee venom might fi nd a therapeutic use in enhancing cytotoxicity of antitumour agent bleomycin.

Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: AnIn VitroStudy

“…The same result was observed in Chinese hamster lung fibroblasts subjected to cotreatment with BV and BLM [25]. Moreover, the inhibitory impact of BV solely on cell viability and proliferation was observed in several types of nontumor isolated cells (i.e., normal human lymphocytes) and cell lines (human embryonic kidney HEK-293 cells and normal Hef fibroblasts), as well as tumor cell lines (human laryngeal HEp-2 and cervical carcinoma HeLa cells and their drug resistant sublines, breast adenocarcinoma MCF-7 cells, colon adenocarcinoma SW620 cells, and glioblastoma A1235 cells) [38, 39].…”

“…However, BLM increases the risk for a life threating lung injury and a wide variety of chromosomal aberrations in noncancerous cells [21]. In addition to its diverse curative applications, BV has been proven to be a useful compound in potentiating the apoptotic killing capacity of some chemotherapeutic agents such as BLM in cancer cell lines [25, 36]. However, Park et al [37] recorded the antiapoptotic effect of BV against tumor necrosis factor (TNF)- α with actinomycin D-induced apoptosis in normal hepatocyte cell lines.…”

“…Previously studied cancer cell lines have illuminated the mitigating effect of BV on the adverse effects of BLM [25]. However, little is known regarding the combined effects of BV and BLM on healthy isolated lymphocytes.…”

Potentiation of a novel palladium (II) complex lethality with bee venom on the human T-cell acute lymphoblastic leukemia cell line (MOLT-4)

“…Orsolic [29], while investigating cytotoxic effects of bee venom applied alone or in combination with the DNA-damaging drug bleomycin on HeLa and V79 cells, found that bleomycin caused a dose-dependent decrease in cell survival. When used with a non-lethal dose of the BV, its lethal effect was potentiated.…”

“…When used with a non-lethal dose of the BV, its lethal effect was potentiated. The author inferred that BV, by preventing repair of damaged DNA, increases bleomycin lethality and inhibited recovery from bleomycin-induced damage [29]. …”