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Gallic acid induces G1 phase arrest and apoptosis of triple-negative breast cancer cell MDA-MB-231 via p38 mitogen-activated protein kinase/p21/p27 axis

Lee, Hsiang-Lina,c; Lin, Chun-Shiangd; Kao, Shao-Hsuanb,d; Chou, Ming-Chiha,c

doi: 10.1097/CAD.0000000000000565

Gallic acid (GA) possesses potential antitumoral activity on different types of malignancies. In this study, we aimed to explore the antitumoral effects of GA on triple-negative breast cancer (TNBC) cells, the breast cancer cells showing resistance to hormonal therapy or HER2 receptor targeting therapy. We observed that GA treatment significantly decreased the cell viability of human TNBC cell line MDA-MB-231 and HS578T in a dose-dependent manner. In addition, GA exerted a relative lower cytotoxicity on noncancer breast fibroblast MCF-10F. Next, we analyzed the changes of cell-cycle distribution in response to GA treatment and found that GA led to an increase of G0/G1 and sub-G1 phase ratio in MDA-MB-231 cells. We further explored the crucial mediators controlling cell cycle and inducing apoptotic signaling, and the findings showed that GA downregulated cyclin D1/CDK4 and cyclin E/CDK2, upregulated p21Cip1and p27Kip1, and induced activation of caspase-9 and caspase-3. In addition, we demonstrated that p38 mitogen-activated protein kinase was involved in the GA-mediated cell-cycle arrest and apoptosis. Collectively, our findings indicate that GA inhibits the cell viability of TNBC cells, which may attribute to the G1 phase arrest and cellular apoptosis via p38 mitogen-activated protein kinase/p21/p27 axis. Thus, we suggest that GA could be beneficial to TNBC treatment.

aDepartment of Surgery

bDepartment of Clinical Laboratory, Clinical Laboratory, Chung Shan Medical University Hospital

cInstitute of Medicine

dInstitute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan

Correspondence to Ming-Chih Chou, MD, PhD, Institute of Medicine, Chung Shan Medical University, No. 110, Section 1, Jianguo North Road, Taichung 402, Taiwan Tel: +886 4 24730022 x11602; fax: +886 4 24723229; e-mail:

Received March 28, 2017

Accepted August 31, 2017

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