Synergistic Effect of Quercetin and Cobalt Ferrite-Graphene Oxide-Based Hyperthermia to Inhibit Expression of Heat Shock Proteins and Induce Apoptosis in Breast Cancer Cells

Combinatorial medicine includes promising therapeutic methods for diseases such as cancer, whereby various biochemical and physical agents are simultaneously used to remove tumors. For example, the effectiveness of hyperthermia as a new technique for cancer therapy, can be enhanced, if it is combined with chemical compounds. Herein, the influence of quercetin as a heat shock protein (HSP) inhibitor on the efficiency of cobalt ferrite-graphene oxide (CoFe2O4-GO) nanoparticles-based hyperthermia was investigated in an in vitro study.

Firstly, the surface of graphene sheets was decorated with CoFe2O4 nanoparticles (5-8 nm) and assayed using transmission electron microscopy (TEM), vibrating-sample magnetometer (VSM) and X-ray diffraction (XRD). The cytotoxic effect of the corresponding co-implementation was then examined in MCF7 cell line with or without hyperthermia by (3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) test for 24, 48 and 72 hrs. In addition, the expression of Bax, Bcl2 and HSP70 genes and the production of radicals were evaluated by Real-Time PCR and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays respectively.

The study showed that the doses associated with the IC50 points for quercetin and the CoFe2O4-GO nanocomposite were 0.02 mg/ml and 0.001 g/ml, respectively. The results showed that the simultaneous treatment of the cancer cells with quercetin, the nanocomposite, and hyperthermia significantly improves the cytotoxicity effect, increases the expression of Bax gene and down-regulates HSP70 and Bcl2 genes. In addition, the greatest attenuation of DPPH free radicals was observed in the corresponding group.

The hybrid treatment of quercetin and the nanoparticle in the presence of hyperthermia could be considered as a promising approach for cancer therapy with minor side effects.