Curcumin increases MDR1 expression in breast cancer MCF-7 and MCF-7/DOX cells through regulating histone acetylation

Abstract

Abstract:

AIM: To study the effect of curcumin on histone acetylation and the expression level of MDR1 (multidrug resistance protein 1) in breast cancer cells MCF-7 and MCF-7/DOX. METHODS: The effect of curcumin on the growth proliferation and sensitivities of doxorubicin against MCF-7 and MCF-7/DOX cells were evaluated by CCK-8 (Cell Counting Kit-8) assay. Real-time PCR and Western blot assays were used to detect the expression levels of MDR1 in MCF-7 and MCF-7/DOX cells. The acetylation levels of MDR1 promoter region related histone H3, H4 were detected by chromatin immunoprecipitation assay. RESULTS:Curcumin inhibited the growth of MCF-7 and MCF-7/DOX cells with the IC50 values of 22.03 μmol/L and 27.46 μmol/L, respectively. The doxorubicin sensitivity of MCF-7 and MCF-7/DOX cells were significantly increased after the treatment of 10 μmol/L curcumin for 72 h, and the values of IC50 were decreased by 57.14% and 54.52% (P<0.05), respectively. After curcumin treatment, MDR1 mRNA levels were (32.90±0.96) and (5.70±0.55) folds increased in MCF-7 and MCF-7/DOX cells (P<0.05), respectively; MDR1 protein levels were (2.26±0.18) and (2.90±0.21) folds increased in MCF-7 and MCF-7/DOX cells (P<0.05), respectively. The MDR1 promoter region related levels of histone H3 and H4 acetylation in MCF-7 and MCF-7/DOX cells were significantly induced by curcumin (P<0.05). CONCLUSION: Curcumin enhances the doxorubicin sensitivities in MCF-7 and MCF-7/DOX cells. Moreover, it induces the MDR1 expression via increasing the MDR1 promoter region related levels of histone H3 and H4 acetylation.

Key words: curcumin, MCF-7, MCF-7/DOX, multidrug resistance protein 1, acetylation

CLC Number:

R965.2

LI Xu, Dai Yi, HUANG Jiafeng, WEN Chunjie, ZOU Zhen, Wu Lanxiang, WANG Guo, ZHOU Honghao. Curcumin increases MDR1 expression in breast cancer MCF-7 and MCF-7/DOX cells through regulating histone acetylation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(5): 512-517.

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