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Mollugin inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2‐overexpressing cancer cells
Author(s) -
Do Minh Truong,
Hwang Yong Pil,
Kim Hyung Gyun,
Na MinKyun,
Jeong Hye Gwang
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24258
Subject(s) - apoptosis , fatty acid synthase , chemistry , cancer research , cancer cell , atp synthase , microbiology and biotechnology , cancer , fatty acid , biology , biochemistry , enzyme , genetics
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.