Administration of Curcumin, Betanin, and CoQ10 combined with nickel oxide, iron superoxide nanoparticles show preventive effects in breast cancer: Effect on apoptosis pathway and MiR-455 expression

Abstract

In the present study, we aimed to evaluate the cytotoxicity and antitumor effect of alone and combined treatment of curcumin, betanin, and coenzyme Q10 (CoQ10) compounds and nickel oxide (NiO) and iron superoxide (Fe2O3) nanoparticles (NPs) on breast cancer cells in vitro and in vivo. The 4T1 breast cancer cells were exposed to different concentrations of Q10, NiO, and Fe2O3 NPs and the inhibitory concentration (IC50) of NPs and compounds and their effect on cell viability In the present study, we aimed to evaluate the cytotoxicity and antitumor effect of alone and combined treatment of curcumin, betanin, and coenzyme Q10 (CoQ10) compounds and nickel oxide (NiO) and iron superoxide (Fe2O3) nanoparticles (NPs) on breast cancer cells in vitro and in vivo. The 4T1 breast cancer cells were exposed to different concentrations of Q10, NiO, and Fe2O3 NPs and the inhibitory concentration (IC50) of NPs and compounds and their effect on cell viability was evaluated by MTT assay. Apoptosis induction in BALB/c mice after treatment with the IC50 concentration of tested compounds was evaluated by flow cytometry. Gene expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The IC50 values for Fe2O3 and NiO NPs were found to be 92.42 µg/mL and 21.49 µg/mL, respectively, and were 0.87 µg/mL, 60.14 µg/mL and 83.47 µg/mL for curcumin, betanin, and CoQ10, respectively. Curcumin was more cytotoxic, whereas Fe2O3 showed lower cytotoxicity than the other compounds in the 4T1 line. All treatments significantly exerted anticancer activity against breast tumors. qRT-PCR analysis revealed that treatment with IC50 concentrations of all alone and combined compounds downregulated the expression of Bcl2 and upregulated Bax in breast tumor. The results revealed a significant reduction in TFAM and MiR-455 expression levels. The combination of aforementioned antitumor agents with Fe2O3 and NiO NPs shows a synergistic impact, as apoptosis induction is boosted by a combination of antitumor agents and NPs, and a higher regulatory impact on gene expression occurs compared with monotherapy.