Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells.
10.4062/biomolther.2017.042
- Author:
Qiuming LIU
1
;
Yali CAO
;
Ping ZHOU
;
Shimin GUI
;
Xiaobo WU
;
Yong XIA
;
Jianhong TU
Author Information
1. Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang, Nanchang 330009, China. caoyali@medmail.com.cn, leecao@yahoo.com
- Publication Type:Original Article
- Keywords:
Breast cancer;
Panduratin A;
Apoptosis;
Cell cycle arrest;
Cyclin D1
- MeSH:
Apoptosis*;
Breast Neoplasms*;
Breast*;
Caspases;
Cell Cycle Checkpoints*;
Cell Cycle*;
Cell Proliferation*;
Cyclin D1;
Cyclins;
Cytochromes c;
Down-Regulation;
Drug Therapy;
Flow Cytometry;
Fluorescent Antibody Technique;
Humans;
Inhibitory Concentration 50;
Insurance Benefits;
MCF-7 Cells;
Phosphotransferases
- From:Biomolecules & Therapeutics
2018;26(3):328-334
- CountryRepublic of Korea
- Language:English
-
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 anti-cancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent 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 dose-dependent (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.
