title: The anti-cancer activity of Antrodia camphorata against human ovarian carcinoma (SKOV-3) cells via modulation of HER-2/neu signaling pathway.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Institute of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Lin
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Juan
authors.forename: K J Senthil
authors.initials: KJ
authors.lastname: Kumar
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Shen
authors.forename: Ssu-Ching
authors.initials: SC
authors.lastname: Chen
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D055491:Antrodia; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045424:Complex Mixtures / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms; D017382:Reactive Oxygen Species / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D045424:Complex Mixtures; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human