Effect of acetyltransferase inhibitor Garcinol on estrogen-promoted proliferation of breast cancer cell line MCF-7 and the related mechanism / 第二军医大学学报

ABSTRACT

Objective: To investigate the effect of acetyltransferase inhibitor Garcinol on estrogen-induced proliferation, cell cycle promotion and apoptosis inhibition of human breast cancer MCF-7 cells and the related mechanism. Methods: The effect of Garcinol on 17β-estradiol (17β-E2)-induced proliferation of MCF-7 cells was investigated using CCK-8 assay, and the optimal concentration of Garcinol was determine according to the inhibition rate. The cell cycle and apoptosis were analyzed by flow cytometry; the nuclear translocation of NF-κB/p65 was examined by immune cell fluorescence. RT-PCR was used to determine the expressions of cyclin D1, Bcl-2 and Bcl-xL mRNA in MCF-7 cells; and the expressions of ac-H3, ac-H4, NF-κB/ac-p65, cyclin D1, Bcl-2, and Bcl-xL protein were determined by Western blotting analysis. Results: Acetyltransferase inhibitor Garcinol inhibited 17β-E2-induced proliferation of MCF-7 cells, arrested MCF-7 cell cycle at G0/G1 phase, and increased the cell apoptosis(P0.05). 17β-E2-induced nuclear translocation of NF-κB/p65 in MCF-7 cells was also significantly inhibited by Garcinol (P<0.01). Garcinol also significantly inhibited 17β-E2-induced transcription and protein expression of cyclin D1, Bcl-2 and Bcl-xL mRNA in MCF-7 cells (P<0.05). Conclusion: 17β-E2-induced proliferation and apoptosis inhibition of MCF-7 cells are associated with elevated acetylation level of histone and nonhistone NF-κB/p65, and acetyltransferase inhibitor Garcinol may inhibit the effect of 17β-E2 by decreasing acetylation, probably through decreasing ac-p65 expression of NF-κB pathway, and subsequently down-regulating cyclin D1,Bcl-2,and Bcl-xL.