M. T. Do, Y. Hwang, Hyung Gyun Kim
May 1, 2013
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Influential Citations
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Quality indicators
Journal
Journal of Cellular Physiology
Abstract
Mollugin is a naphthohydroquine found in the roots of Rubia cordifolia, and has been reported to have a variety of biological activities, including anti‐inflammatory and apoptotic effects. In the present study, we investigated the molecular mechanisms by which mollugin exerts anti‐tumor effect in HER2‐overexpressing cancer cells. Our results showed that mollugin exhibited potent inhibitory effects on cancer cell proliferation, especially in HER2‐overexpressing SK‐BR‐3 human breast cancer cells and SK‐OV‐3 human ovarian cancer cells in a dose‐ and time‐dependent manner without affecting immortalized normal mammary epithelial cell line MCF‐10A. Furthermore, we found that a blockade of Akt/SREBP‐1c signaling through mollugin treatment significantly reduced FAS expression and subsequently suppressed cell proliferation and induced apoptosis in HER2‐overexpressing cancer cells. Mollugin treatment caused a dose‐dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF‐κB activation. The combination of mollugin with a MEK1/2 inhibitor may be required in order to achieve optimal efficacy in HER2‐overexpressing cancers. These data provide evidence that mollugin inhibits proliferation and induces apoptosis in HER2‐overexpressing cancer cells by blocking expression of the FAS gene through modulation of a HER2/Akt/SREBP‐1c signaling pathway. Our findings suggest that mollugin is a novel modulator of the HER2 pathway in HER2‐overexpressing cancer cells with a potential role in the treatment and prevention of human breast and ovarian cancer with HER2 overexpression. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.