Anthocyanins Isolated fromVitis coignetiae PulliatEnhances Cisplatin Sensitivity in MCF-7 Human Breast Cancer Cells through Inhibition of Akt and NF-kappa B Activation

Abstract

Anthocyanins isolated fromVitis coignetiae Pulliat(Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-kappa B which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-kappa B and p-I kappa B and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-kappa B and p-I kappa B in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-alpha treatment, AIMs augmented CDDP efficacy with inhibition of NF-kappa B activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-kappa B activity of MCF-7 cells that show relative intrinsic CDDP resistance.