Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 59, Issue 5, Pages 1996-2003Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf103656v
Keywords
gallic acid; cell cycle arrest; MCF-7; p27(KiP1); p21(Cip1); Skp2
Funding
- Council of Agriculture, Executive Yuan, Taiwan [97AS-3.1.3-FD-Z1]
- Chung Shan Medical University Hospital [CSH-2011-C-009]
Ask authors/readers for more resources
Gallic acid (GA), 3,4,S-trihydroxybenzoic acid, is a natural polyphenolic acid and widely found in gallnuts, tea leaves and various fruits. Previous studies have shown that GA possesses anti-inflammatory, antiallergic and anticarcinogenic activity. In the present study, we aim to investigate the antitumor effects of GA on breast cancer cell. Our results revealed that GA treatment significantly reduced the cell growth of human breast cancer cell MCF-7 in a dose-dependent manner. Further flow cytometric analysis showed that GA induced significant G2/M phase arrest but slightly affected the population of sub-G1MCF-7 cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, CDK2, cyclin B1 and cdc2/CDK1 were diminished; in contrast, levels of the negative regulators p27(Kip1) and p21(Cip1) were increased by GA treatment. Additionally, Skp2, a specific ubiquitin E3 ligase for polyubiquitination of p27(Kip1) was reduced by GA treatment. Further investigation showed that GA attenuated Skp2-p27(Kip1) association and diminished polyubiquitination of p27(Kip1) in MCF-7 cells. Moreover, knockdown of p27(kip1) but not p21(Cip1) significantly alleviated GA-induced accumulation of G2/M phase. These findings indicate that GA may upregulate p27(Kip1) level via disruption of 22.7(Kip1)/Skp2 association and the consequent degradation of p27(Kip1) by proteosome, leading to G2/M phase arrest of MCF-7 cell. It is suggested that GA should be beneficial to treatment of breast cancer and p27(Kip1)-deficient carcinomas.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available