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Mollugin Inhibits Proliferation and Induces Apoptosis by Suppressing Fatty Acid Synthase in HER2-overexpressing Cancer Cells

Mollugin Inhibits Proliferation and Induces Apoptosis by Suppressing Fatty Acid Synthase in HER2-overexpressing Cancer Cells

Minh Truong Do, Yong Pil Hwang, Hyung Gyun Kim, Minkyun Na, Hye Gwang Jeong

J Cell Physiol. 2013 May;228(5):1087-97.

PMID: 23065756

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP55481884	Mollugin		55481-88-4	Price

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