Novel effect and the mechanistic insights of fruiting body extract of medicinal fungus Antrodia cinnamomea against T47D breast cancer

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• 作者：Kuang-Ming Shang^a ; ¹ ; Tzu-Hsuan Su^a ; ¹ ; Wai Leng Lee^b ; Wen-Wei Hsiao^c ; Ching-Yi Chiou^a ; Bing-Ying Ho^a ; Sheng-Yang Wang^d ; Lie-Fen Shyur^a ; ^e ; ^f ; ^{lfshyur@ccvax.sinica.edu.tw} ; ^{jaclyn@gate.sinica.edu.tw}
• 关键词：Antrodia cinnamomea ; Tamoxifen ; Anti-angiogenesis ; ER+ T47D breast cancer ; Dehydroeburicoic acid
• 刊名：Phytomedicine
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：24
• 期：Complete
• 页码：39-48
• 全文大小：3038 K
• 卷排序：24

文摘

Tamoxifen, an anti-oestrogenic drug for estrogen receptor positive (ER+) breast cancer, was observed to stimulate tumor growth or drug resistance in patients. Antrodia cinnamomea (AC), a precious medicinal fungus has been traditionally used as a folk remedy for cancers in Asian countries. The objective of this study was to investigate the bioefficacy and the underlying molecular mechanisms of the AC fruiting bodies extracts (AC-3E) against human ER+ T47D breast cancer cells, and compare the effect with that of tamoxifen.MethodsCell proliferation, migration, TUNEL assay, western blotting, time-lapse confocal microscopy analyses, chorioallantoic membrane assay, and a xenograft BALB/c nude mouse system were used in this study. Chemical fingerprinting of AC-3E was established using LC-MS.ResultsAC-3E attenuated T47D breast cancer cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators, and inducing apoptosis. AC-3E also effectively inhibited tube-like structures of endothelial cells, blood vessel branching and microvessel formation ex vivo and in vivo. Significant preventive and therapeutic effects against T47D mammary tumor growth of AC-3E was observed comparable or superior to tamoxifen treatment in xenograft BALB/c nude mice. Dehydroeburicoic acid (2) was characterized as the main chemical constituent in AC-3E against breast cancer.ConclusionThis study suggests that AC-3E extracts can be employed as a double-barreled approach to treat human ER+ breast cancer by attacking both cancer cells and tumor-associated blood vessel cells.