The Effect Of Quercetin And Doxorubicin Combination In Inhibiting Resistance In MCF-7 Cell

Sufi DESRINI, department of pharmacology, Medical Faculty,Islamic University of Indonesia, Indonesia
MUSTOFA M. 2 , SHOLIKHAH E. 2

1 Departement of Pharmacology, Faculty of Medicine , Islamic University of Indonesia, Jl. Kaliurang km 14,5 Sleman Yogjakarta, Indonesia 55584
2 Department of Pharmacology and Toxicology, Faculty of Medicine, Universitas Gadjah Mada, Jl. Farmako, Sekip Utara, Yogjakarta, Indonesia 55281

PURPOSE. This purpose of this study to investigate the effect of quercetin and doxorubicin  combination in inhibiting the development of resistance in MCF-7 cell.
METHODS. Doxorubicin-resistant MCF-7 cell were developed from the parent MCF-7 cell by giving doxorubicin concentration below the IC50 value of parental MCF-7 cell, twice a week for a period of 25 days. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) citotoxicity assay and flowcytometry assay were performed to investigate P-glycoprotein level as a marker of doxorubicin resistance developed in MCF-7. The inhibitory effect of resistance was evaluated via exposured  MCF-7 cells to 75 nM doxorubicin and 750 nM quercetin combination in the same manner with resistance induction. MTT citotoxicity assay and flowcytometry assay were performed to investigate the degree of resistance and inhibition of resistance development.
RESULTS. Exposure of MCF-7 cells to 75 nM doxorubicin reduce the sensitivity of the cancer cells and enhance P-glycoprotein level. This effect was statistically-significant (95% CI;p<0,05). The combination  of 750 nM quercetin and 75 nM doxorubicin (MCF-7 cells/dox75q750) significantly increase  sensitivity of MCF-7 cell to doxorubicin (p<0,05) and decrease in P-gp expression (p> 0,05).
CONCLUSIONS. The combination of quercetin and doxorubicin  have potency to inhibit the development of doxorubicin-acquired resistance  MCF-7 cell  by increasing cell sensitivity and reducing P-gp expression level.
KEYWORDS. MCF-7 cell line, Resistance, Quercetin, Doxorubicin, P-gp
FUNDING SOURCE. This study was financed partly by HPEQ (Health Professional Education Quality Project)-Dikti through Faculty of Medicine-UII who had provided scholarship.