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

Abstract

Combining chemotherapy with radiotherapy represents a key oncology strategy for a more comprehensive attack toward cancers and improves treatment outcome for various solid tumor malignancies. The present study aims to evaluate the synergistic antitumor effect of γ-radiation together with gallium trichloride (GaCl3) and/or doxorubicin (DOX) against solid Ehrlich carcinoma (EC) in female mice. GaCl3 (300 mg/kg body weight (b.w.)) was administered by gavages daily on the seventh day after tumor inoculation, while the cytotoxic drug DOX (4 mg/kg b.w.) was administered intraperitoneally once a week. Whole-body γ-radiation was carried out at a dose 2 Gy once a week. Biochemical analysis showed that solid EC induced a significant increase in malondialdehyde (MDA) content with a significant decrease in the antioxidant state (glutathione peroxidase (GPx) and catalase (CAT) activities) and depleted serum iron concentration compared to normal control. Moreover, a significant increase was observed in calcium level and caspase-3 concentrations in both serum and tumor homogenate respectively associated with a significant alteration in heart, liver, and kidney functions, as compared to control. Treatment of EC-bearing mice with GaCl3and/or DOX combined with γ-radiation exposure significantly reduced tumor volume and displayed a significant improvement in most studied markers which may indicate a synergistic effect of this combination against organ dysfunction and cellular injury. The histopathologically investigation showed that treatment of animals bearing EC with GaCl3and/or DOX with γ-radiation exposure showed shrinkage in tumor lesions and wide zones of apoptotic cells with signs of regenerations. It was concluded that the combination of GaCl3and/or DOX with γ-radiation exposure resulted in super-additive cytotoxic effects on treatment of cancer cells.

Evaluation of the antitumor effects of gallium trichloride and doxorubicin in cancer treatment

“…Serum CPK, AST and LDH activities are used clinically to evaluate and diagnose cardiac dysfunction and disease. The present data showed that, serum AST, CPK and LDH activities were significantly elevated in EC and EC+ Dox groups compared to normal control group and these results correlate well with others [39,44] . The data presented here showed that, the administration of GaCl 3 alone or combined with Dox showed marked decrease in the activities of serum AST, CPK and LDH compared to both EC and EC+Dox groups.…”

Anticancer redox activity of gallium nanoparticles accompanied with low dose of gamma radiation in female mice

“…Administration of GaNPs and/or R exposure to tumor-bearing mice significantly decreased calcium concentration in liver and tumor tissues in the treated groups (EC + R, EC + GaNPs, and EC + GaNPs + R) compared to EC group, and this result is consistent with others. 51,52 Gallium appears to be a uniquely acting agent for treatment of bone-resorptive conditions reducing accelerated bone loss in patients with cancer. In contrast to other calcium-saving drugs, gallium enhances calcium and phosphorus content of the bone and has direct, non-cytotoxic effects on osteoclasts at markedly low doses, and it is well established that the mechanism involves gallium insertion into the hydroxyapatite matrix protecting it from resorption and improving biomechanical properties of the skeletal system.…”

“…In contrast to other calcium-saving drugs, gallium enhances calcium and phosphorus content of the bone and has direct, non-cytotoxic effects on osteoclasts at markedly low doses, and it is well established that the mechanism involves gallium insertion into the hydroxyapatite matrix protecting it from resorption and improving biomechanical properties of the skeletal system. 52 Low-dose ionizing radiation suppressed intracellular Ca 2+ influx. It was found that vRBL-2H3 cell line exposed to ionizing radiation in the range of 0.01–0.5 Gy showed decrease in the levels of calcium influx in a dose-dependent manner.…”

Anticancer and Apoptogenic Effect of Graviola and Low-Dose Radiation in Tumor Xenograft in Mice

“…EAC cells are of mammary origin. 16 The viability of the cells was 99% as judged by trypan blue exclusion assay. The xenograft model of Ehrlich solid tumor (EST) was induced in female Swiss albino mice by viable EAC cells (about 2.5 × 106/mouse) in 0.2 mL isotonic saline implanted subcutaneously (sc) into the right thigh of the hind limb of each mouse.…”