title: Antrodia salmonea induces G2cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athymic nude mice.
abstract: BACKGROUND
  Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects.
  
  
  METHODS
  In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model.
  
  
  RESULTS
  AS (0-200μg/mL) treatment significantly induced G2cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G2cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest.
  
  
  CONCLUSIONS
  Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer.
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chia-Ting
authors.initials: CT
authors.lastname: Chang
authors.affiliation: Department of Cosmeceutics,Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
authors.affiliation: Department of Cosmeceutics,Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Varadharajan
authors.initials: V
authors.lastname: Thiyagarajan
authors.affiliation: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, 40402 Taichung, Taiwan.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Pei-Jane
authors.initials: PJ
authors.lastname: Huang
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan. Electronic address: hlyang@mail.cmu.edu.tw.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D055491:Antrodia; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D052246:Cyclooxygenase 2 Inhibitors; D011065:Poly(ADP-ribose) Polymerases
keywords: Antrodia salmonea; Apoptosis; Autophagy; Breast cancer; G(2) cell-cycle arrest; MDA-MB-231cells