Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

  • Liu, Qiuming (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang) ;
  • Cao, Yali (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang) ;
  • Zhou, Ping (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang) ;
  • Gui, Shimin (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang) ;
  • Wu, Xiaobo (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang) ;
  • Xia, Yong (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang) ;
  • Tu, Jianhong (Department of Breast Surgery, Breast Cancer Institute, The Third Hospital of Nanchang)
  • Received : 2017.02.28
  • Accepted : 2017.08.28
  • Published : 2018.05.01
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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 dose-dependent inhibition of cell growth with an $IC_{50}$ of $15{\mu}M$ 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 $p21^{WAF1/Cip1}$ 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.

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References

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