Synergistic efficacy of γ-radiation together with gallium trichloride and/or doxorubicin against Ehrlich carcinoma in female mice

Guided treatments with nanoparticles and radiotherapy are a new approach in cancer therapy. This study evaluated the beneficial antitumor effects of γ-radiation together with gallium nanoparticles against solid Ehrlich carcinoma in female mice. Gallium nanoparticles were biologically synthesized using Lactobacillus helveticus cells. Transmission electron microscopy showed gallium nanoparticles with size range of 8−20 nm. In vitro study of gallium nanoparticles on MCF-7 revealed IC50 of 8.0 μg. Gallium nanoparticles (0.1 mg/kg body weight) were injected intraperitoneally daily on the seventh day of Ehrlich carcinoma cells inoculation. Whole-body γ-radiation was carried out at a single dose of 0.25 Gy on eighth day after tumor inoculation. Biochemical analysis showed that solid Ehrlich carcinoma induced a significant increase in alanine aminotransferase activity and creatinine level in serum, calcium, and iron concentrations in liver tissue compared to normal control. Treatment of Ehrlich carcinoma–bearing mice with gallium nanoparticles and/or low dose of γ-radiation exposure significantly reduced tumor volume, decreased alanine aminotransferase and creatinine levels in serum, increased lipid peroxidation, and decreased glutathione content as well as calcium and iron concentrations in liver and tumor tissues with intense DNA fragmentation accompanied compared to untreated tumor cells. Moreover, mitochondria in the treated groups displayed a significant increase in Na+/K+-ATPase, complexes II and III with significant reduction in CYP450 gene expression, which may indicate a synergistic effect of gallium nanoparticles and/or low dose of γ-radiation combination against Ehrlich carcinoma injury, and this results were well appreciated with the histopathological findings in the tumor tissue. We conclude that combined treatment of gallium nanoparticles and low dose of gamma-radiation resulted in suppressive induction of cytotoxic effects on cancer cells.

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Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-Irradiated Solid Ehrlich Carcinoma-Bearing Mice

Integrative Cancer Therapies ◽

10.1177/1534735420944476 ◽

2020 ◽

Vol 19 ◽

pp. 153473542094447

Author(s):

Nermeen M. El Bakary ◽

Asmaa Z. Alsharkawy ◽

Zeinab A. Shouaib ◽

Emad M. S. Barakat

Keyword(s):

Ehrlich Ascites Carcinoma ◽

Bee Venom ◽

Whole Body ◽

Major Constituent ◽

Ehrlich Carcinoma ◽

Γ Radiation ◽

Ehrlich Ascites ◽

Tnf Α ◽

Therapeutic Protocols

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.

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