Hesperidin as a preventive resistance agent in MCF–7 breast cancer cells line resistance to doxorubicin.

Febriansah, Rifki; Dyaningtyas, Dewi P.P.; Sarmoko, null; Nurulita, Nunuk Aries; Meiyanto, Edy; Nugroho, Agung Endro

Objective To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin. Methods The cytotoxic properties, 50% inhibition concentration (IC 50 ) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp. Results Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC 50 value of 11 μmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect ( CI >1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration. Conclusions Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC 50 of 11 μmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.

HESPERIDIN; DRUG resistance; CELL-mediated cytotoxicity; DOXORUBICIN; GENE expression; P-glycoprotein; BIOLOGICAL assay

Asian Pacific Journal of Tropical Biomedicine, 2014, Vol 4, Issue 3, p228

2221-1691

Academic Journal

10.1016/S2221-1691(14)60236-7