1. The anti-cancer activity of Antrodia camphorata against human ovarian carcinoma (SKOV-3) cells via modulation of HER-2/neu signaling pathway.
- Author
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Yang, Hsin-Ling, Lin, Kai-Yuan, Juan, Ying-Chen, Kumar, K.J. Senthil, Way, Tzong-Der, Shen, Pei-Chun, Chen, Ssu-Ching, and Hseu, You-Cheng
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OVARIAN tumors , *REACTIVE oxygen species , *ALTERNATIVE medicine , *ANTINEOPLASTIC agents , *BIOLOGICAL assay , *BIOLOGICAL models , *CELL death , *CELLULAR signal transduction , *DOSE-effect relationship in pharmacology , *FLOW cytometry , *FUNGI , *IMMUNOBLOTTING , *MICROSCOPY , *WESTERN immunoblotting , *WOMEN'S health , *STATISTICAL significance , *DESCRIPTIVE statistics , *IN vitro studies , *PHARMACODYNAMICS , *PREVENTION - Abstract
Abstract: Ethnopharmacological relevance: 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. Materials and methods: 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. Results: 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. Conclusions: These results suggest that AC may exert anti-tumor activity against human ovarian carcinoma by suppressing HER-2/neu signaling pathways. [Copyright &y& Elsevier]
- Published
- 2013
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