Pathological angiogenesis and apoptosis evasion are common hallmarks of cancer. The present work was an endeavor to evaluate the influence of bee venom (BV) or its major constituent melittin (MEL) as antiapoptotic and angiogenic regulator modifier on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. BV (0.56 mg/kg/day) and MEL (500 µg/kg body weight/day) were injected intraperitoneally to mice bearing 1 cm3 solid tumor of Ehrlich ascites carcinoma (EAC) for 21 consecutive days. Mice were whole-body exposed to 1 Gray (Gy) of γ-radiation (2 fractionated doses). Treatment with BV or MEL markedly suppresses the proliferation of tumor in EAC mice. The concentrations of m-RNA for angiogenic factors (TNF-α, VEGF) as well as MMPs 2 and 9 activities and NO concentration were significantly decreased, combined with improvements in apoptotic regulators (caspase-3 activity) and normal cells redox tone (catalase and free radicals content) compared with EAC mice. Moreover, the histopathological investigation confirms the improvement exerted by BV or MEL in the EAC mice group or EAC + R group. Exposure to γ-radiation sustained the modulatory effect of BV on tumor when compared with EAC + BV mice. Convincingly, the role of BV or MEL as a natural antiangiogenic in the biological sequelae after radiation exposure is verified. Hence, BV and its major constituent MEL might represent a potential therapeutic strategy for increasing the radiation response of solid tumors.

The rising interest in innovative methods of cancer immunotherapy has prompted research into the immunomodulatory mechanisms of natural and synthetic substances. The goal of this study was to assess chrysin immune-stimulating and pro-apoptotic effects on tumor growth and cell susceptibility to ionizing radiation in order to improve cancer therapy. Chrysin (20 mg/kg/day) was intraperitoneally injected to mice bearing 1 cm3 solid tumor of Ehrlich ascites carcinoma (EAC) for 21 consecutive days. Mice were whole body exposed to 1 Gy of gamma radiation (2 fractionated dose 0.5 Gy each). Treatment with chrysin dramatically reduces tumor proliferation in EAC mice; furthermore, IFN-γ activity is significantly reduced when compared to EAC mice. When compared to EAC mice, the expression of TNF-α, free radicals, and nitric oxide (NO) levels were considerably reduced, along with improvements in apoptotic regulators (caspase-3 activity). Moreover, the histopathological investigation confirms the improvement exerted by chrysin even in the EAC mice group or the EAC + R group. What is more, exposure to gamma radiation sustained the modulatory effect of chrysin on tumor when compared with EAC + Ch mice. Hence, chrysin might represent a potential therapeutic strategy for increasing the radiation response of solid tumor.