Biomol Ther.  2018 May;26(3):328-334. 10.4062/biomolther.2017.042.

Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

• Liu Q
• Cao Y
• Zhou P
• Gui S
• Wu X
• Xia Y
• Tu J

• KMID: 2421743
• DOI: http://doi.org/10.4062/biomolther.2017.042

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.

Keyword

Breast cancer; Panduratin A; Apoptosis; Cell cycle arrest; Cyclin D1

MeSH Terms

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
Caspases
Cyclin D1
Cyclins
Cytochromes c
Phosphotransferases