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

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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:	陳師慶;Hseu, You Cheng;Chen, Ssu-Ching;Lin, Kai-Yuan;Cho, Hsin-Ju;Juan, Ying-Chen;Kumar, K. J. Senthil;Way, Tzong-Der;Yang, Hsin-Ling;Lee, Chuan-Chen;Hsu, Li-Sung
Contributors:	生醫理工學院生命科學系
Keywords:	1-Phosphatidylinositol 3-kinase;Acetylcysteine;AKT protein;Antioxidants;Antitumor activity;Apoptosis;Bcl-2 protein;Breast cancer;Cancer therapies;Caspase;Caspase-3;Cell culture;Cell death;Cell growth;Colorectal cancer;Cyclin D1;Cyclin E;Cyclin-dependent kinase 4;Cytochrome c;Cytotoxicity;DNA fragmentation;ErbB-2 protein;Fermentation;Kinases;Mitochondrial DNA;Penicillin;Phosphorylation;Poly(ADP-ribose) polymerase;Reactive oxygen species;Signal transduction;Tumors
Date:	2012-07-16
Issue Date:	2026-04-23 11:13:08 (UTC+8)
Publisher:	Cairo, Egypt: Hindawi Publishing Corporation
Abstract:	摘要： 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. 其他題名： Evid Based Complement Alternat Med 出版者： Cairo, Egypt: Hindawi Publishing Corporation 出版日期： 2012-01-01 出處： Evidence-based complementary and alternative medicine, 2012-01, Vol.2012 (2012), p.1-15 資源來源： ProQuest Open Access Content Collection 版權： Copyright © 2012 Chuan-Chen Lee et al. 版權： Copyright © 2012 Chuan-Chen Lee et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0 版權： Copyright © 2012 Chuan-Chen Lee et al. 2012 識別號： ISSN: 1741-427X 識別號： ISSN: 1741-4288 識別號： EISSN: 1741-4288 識別號： DOI: 10.1155/2012/702857 識別號： PMID: 22701509
Appears in Collections:	[Department of Life Science] journal & Dissertation

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