Osthole Suppresses Fatty Acid Synthase Expression in HER2-Overexpressing Breast Cancer Cells through Modulating Akt/mTOR Pathway

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• 作者：Victor Chia-Hsiang Lin ; Chun-Hung Chou ; Ying-Chao Lin ; Jia-Ni Lin ; Chien-Chih Yu ; Chih-Hsin Tang ; Hui-Yi Lin ; Tzong-Der Way
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2010
• 出版时间：April 28, 2010
• 年：2010
• 卷：58
• 期：8
• 页码：4786-4793
• 全文大小：902K
• 年卷期：v.58,no.8(April 28, 2010)
• ISSN：1520-5118

文摘

While fatty acid synthase (FASN) has been shown to be expressed in many human solid tumors, FASN has also been identified in preneoplastic lesions. HER2, which has also been identified in preneoplastic breast lesions, has been shown to upregulate FASN expression. Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a traditional Chinese medicine, was found to be effective in suppressing FASN expression in HER2-overexpressing breast cells. Osthole preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Moreover, osthole inhibited the phosphorylation of Akt and mTOR. The use of Akt-overexpression revealed that the modulation of Akt and mTOR was required for osthole-induced FASN suppression. Finally, we showed that osthole could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells. These results suggested that osthole has the potential to advance as chemopreventive or chemotherapeutic agent for cancers that overexpress HER2.