Inhibition of Cell Growth and Induction of Apoptosis by Antrodia camphorata in HER-2/neu-Overexpressing Breast Cancer Cells through the Induction of ROS, Depletion of HER-2/neu, and Disruption of the PI3K/Akt Signaling Pathway

doi:10.1155/2012/702857

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Title:	Inhibition of Cell Growth and Induction of Apoptosis by Antrodia camphorata in HER-2/neu-Overexpressing Breast Cancer Cells through the Induction of ROS, Depletion of HER-2/neu, and Disruption of the PI3K/Akt Signaling Pathway
Authors:	Lee, Chuan-Chen Yang, Hsin-Ling Way, Tzong-Der Kumar, K.J.Senthil Juan, Ying-Chen Cho, Hsin-Ju Lin, Kai-Yuan Hsu, Li-Sung Chen, Ssu-Ching Hseu, You-Cheng
Contributors:	中山醫學大學
Date:	2012
Issue Date:	2015-07-02T09:39:52Z (UTC)
ISSN:	1741-427X
Abstract:	Previously, we demonstrated that a submerged fermentation culture of Antrodia camphorata (AC) promotes cell-cycle arrest and apoptosis in human estrogen receptor-positive/negative breast cancer cells. However, whether AC is effective against HER-2/neu-overexpressing breast cancers has not been thoroughly elucidated. In the present study, we showed that AC exhibited a significant cytotoxic effect against HER-2/neu-overexpressing MDA-MB-453 and BT-474 cells. Immunoblot analysis demonstrated that HER-2/neu and their tyrosine phosphorylation were inhibited by AC in a dose-dependent manner. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas antioxidant N-acetylcysteine (NAC) significantly prevented AC induced HER-2/neu depletion and cell death, which directly indicates that AC-induced HER-2/neu depletion and cell death was mediated by ROS generation. Also, AC significantly downregulated the expression of cyclin D1, cyclin E, and CDK4 followed by the suppression of PI3K/Akt, and their downstream effectors GSK-3β and β-catenin. Notably, AC-treatment induced apoptotic cell death, which was associated with sub-G1 accumulation, DNA fragmentation, mitochondrial dysfunction, cytochrome c release, caspase-3/-9 activation, PARP degradation, and Bcl-2/Bax dysregulation. Assays for colony formation also confirmed the growth-inhibitory effects of AC. This is the first report confirming the anticancer activity of this potentially beneficial mushroom against human HER-2/neu-overexpressing breast cancers.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/11001 http://dx.doi.org/10.1155/2012/702857
Relation:	Evidence-Based Complementary and Alternative Medicine Volume 2012 (2012), Article ID 702857, 15 pages
Appears in Collections:	[生化微生物免疫研究所] 期刊論文

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