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Apoptosis and necrosis as possible mechanisms for antitumor activity of bee venom

Based on the observation that melittin, a major component of bee venom, is by far a more potent inhibitor of calmodulin activity and a potent inhibitor of cell growth and clonogenicity, possible tumor growth&#8211; and metastasis-inhibiting effects of bee venom in vivo or in vitro were studied. Tumor was a transplantable mammary carcinoma (MCa) of spontaneous origin. Tumor in footpad was generated by 1 x 105 tumor cells, while intravenous (iv) injection 105 tumor cells generated metastases in the lungs. Bee venom was injected into mice subcutaneously (sc) at doses of 150, 300, 600 &#61549; g/mouse or 75 and 150 &#61549; g/mouse intravenously (iv), respectively. When tumor cells were injected into footpad immediately after bee venom, the growth of tumor was suppressed irrespective of the venom dose administered. The survival of treated mice was also prolonged. The number of lung metastases in mice treated iv with bee venom was significantly lower (p<0.001) compared to control. However, neither dose of bee venom given sc reduced the number of lung metastases, indicating that antitumor effect of the venom could be highly dependent on close contact of its components with tumor cells, as shown by in vitro studies with HeLa and MCa cells.

Bee venom; tumor; metastases; cytotoxic effects; apoptosis; necrosis

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