Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways

Abstract

Improving radiation effect on tumor cells using radiosensitizers is gaining traction for improving chemoradiotherapy. This study aimed to evaluate copper nanoparticles (CuNPs) synthesized using chrysin as radiosensitizer with γ-radiation on biochemical and histopathological approaches in mice bearing Ehrlich solid tumor. CuNPs were characterized with irregular round sharp shape with size range of 21.19–70.79 nm and plasmon absorption at 273 nm. In vitro study on MCF-7 cells detected cytotoxic effect of CuNPs with IC ₅₀ of 57.2 ± 3.1 μg. In vivo study was performed on mice transplanted with Ehrlich solid tumor (EC). Mice were injected with CuNPs (0.67 mg/kg body weight) and/or exposed to low dose of gamma radiation (0.5 Gy). EC mice exposed to combined treatment of CuNPs and radiation showed a marked reduction in tumor volume, ALT and CAT, creatinine, calcium, and GSH, along with elevation in MDA, caspase-3 in parallel with inhibition of NF-κB, p38 MAPK, and cyclin D ₁ gene expression. Comparing histopathological findings of treatment groups ends that combined treatment was of higher efficacy, showing tumor tissue regression and increase in apoptotic cells. In conclusion, CuNPs with a low dose of gamma radiation showed more powerful ability for tumor suppression via promoting oxidative state, stimulating apoptosis, and inhibiting proliferation pathway through p38MAPK/NF-κB and cyclinD1.