Biomol Ther  
Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells
Qiuming Liu, Yali Cao*, Ping Zhou, Shimin Gui, Xiaobo Wu, Yong Xia and Jianhong Tu
Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang, Nanchang 330009, China
E-mail: caoyali@medmail.com.cn; leecao@yahoo.com
Tel: +079186615534, Fax: +079186615534
Received: February 28, 2017; Revised: May 18, 2017; Accepted: August 28, 2017; Published online: January 5, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dosedependent inhibition of cell growth with an IC50 of 15 μM and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dosedependent (i) induction of p21WAF1/Cip1 and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.
Keywords: Breast cancer, Panduratin A, Apoptosis, Cell cycle arrest, Cyclin D1


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