Lee Hsiang-Lin, Lin Chun-Shiang, Kao Shao-Hsuan, Chou Ming-Chih
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.
Anticancer Drugs. 2017 Nov;28(10):1150-1156. 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 p21and p27, 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.
没食子酸（GA）对不同类型的恶性肿瘤具有潜在的抗肿瘤活性。在本研究中，我们旨在探讨GA对三阴性乳腺癌（TNBC）细胞的抗肿瘤作用，这类乳腺癌细胞对激素疗法或HER2受体靶向疗法具有抗性。我们观察到，GA处理以剂量依赖性方式显著降低了人TNBC细胞系MDA-MB-231和HS578T的细胞活力。此外，GA对非癌性乳腺成纤维细胞MCF-10F的细胞毒性相对较低。接下来，我们分析了GA处理后细胞周期分布的变化，发现GA导致MDA-MB-231细胞中G0/G1期和亚G1期比例增加。我们进一步探究了控制细胞周期和诱导凋亡信号的关键介质，结果表明，GA下调细胞周期蛋白D1/细胞周期蛋白依赖性激酶4（CDK4）和细胞周期蛋白E/细胞周期蛋白依赖性激酶2（CDK2），上调p21和p27，并诱导半胱天冬酶-9（caspase-9）和半胱天冬酶-3（caspase-3）激活。此外，我们证明p38丝裂原活化蛋白激酶参与了GA介导的细胞周期阻滞和凋亡。总的来说，我们的研究结果表明，GA抑制TNBC细胞的细胞活力，这可能归因于通过p38丝裂原活化蛋白激酶/p21/p27轴导致的G1期阻滞和细胞凋亡。因此，我们认为GA可能对TNBC治疗有益。
