| 摘要: | 摘要: Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicinal fungus. However, the anticancer activity of AC against human HER-2/neu-overexpressing ovarian cancers is poorly understood. The aim of this study is to investigate whether a submerged fermentation culture of AC can inhibit human ovarian carcinoma cell (SKOV-3) proliferation by suppressing the HER-2/neu signaling pathway. Cell viability, colony formation, DCFH-DA fluorescence microscopy, western blotting, HER-2/neu immunofluorescence imaging, flow cytometry, and TUNEL assays were carried out to determine the anti-cancer effects of AC. MTT and colony formation assays showed that AC induced a dose-dependent reduction in SKOV-3 cell growth. Immunoblot analysis demonstrated that HER-2/neu activity and tyrosine phosphorylation were significantly inhibited by AC. Furthermore, AC treatment significantly inhibited the activation of PI3K/Akt and their downstream effector β-catenin. We also observed that AC caused G2/M arrest mediated by down-regulation of cyclin D1, cyclin A, cyclin B1, and Cdk1 and increased p27 expression. Notably, AC induced apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9/-3 activation, PARP degradation, and Bcl-2/Bax dysregulation. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented AC-induced cell death, HER-2/neu depletion, PI3K/Akt inactivation, and Bcl-2/Bax dysregulation, indicating that AC-induced cell death was mediated by ROS generation. These results suggest that AC may exert anti-tumor activity against human ovarian carcinoma by suppressing HER-2/neu signaling pathways. The submerged fermentation culture of Antrodia camphorata (AC) could inhibit the human ovarian carcinoma (SKOV-3) proliferation by suppressing the HER-2/neu signaling pathway [Display omitted] . 其他題名: J Ethnopharmacol 出版者: Ireland: Elsevier Ireland Ltd 出版日期: 2013-06-21 出處: Journal of Ethnopharmacology, 2013-06, Vol.148 (1), p.254-265 版權: 2013 Elsevier Ireland Ltd 版權: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved. 識別號: ISSN: 0378-8741 識別號: ISSN: 1872-7573 識別號: EISSN: 1872-7573 識別號: DOI: 10.1016/j.jep.2013.04.023 識別號: PMID: 23619020 |