Effect of acetyltransferase inhibitor Garcinol on estrogen-promoted proliferation of breast cancer cell line MCF-7 and the related mechanism
10.3724/SP.J.1008.2014.00714
- Author:
Xia YE
1
Author Information
1. Department of Pathophysiology, Laboratory for Stem Cell and Tissue Engineering, College of Basic Medicine, Chongqing Medical University
- Publication Type:Journal Article
- Keywords:
Acetylation;
Breast neoplasms;
Garcinol;
Histones;
NF-κB
- From:
Academic Journal of Second Military Medical University
2014;35(7):714-721
- CountryChina
- Language:Chinese
-
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(P<0.01). 17β-E2 increased the expressions of ac-H3, ac-H4 and NF-κB/ac-p65 protein in MCF-7 cells(P<0.01, P<0.05, P<0.01), while Garcinol significantly inhibited the increase of ac-H3 and NF-κB/ac-p65 (P<0.01) but not ac-H4(P>0.05). 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.
