title: The anti-tumor activity of Antrodia salmonea in human promyelocytic leukemia (HL-60) cells is mediated via the induction of G₁ cell-cycle arrest and apoptosis in vitro or in vivo.
abstract: BACKGROUND
  The medicinal mushroom Antrodia salmonea has been used as a traditional Chinese medicine and has demonstrated antioxidant and anti-inflammatory effects.
  
  
  METHODS
  In the present study, we examined the anti-tumor activity of the fermented culture broth of Antrodia salmonea (AS) in vitro and in vivo and revealed its underlying molecular mechanism of action.
  
  
  RESULTS
  Treatment of human promyelocytic leukemia (HL-60) cells with AS (50-150 μg/mL) significantly reduced cell viability and caused G1 arrest via the inhibition of cell-cycle regulatory proteins, including cyclin D1, CDK4, cyclin E, cyclin A, and phosphorylated retinoblastoma protein (p-Rb). Furthermore, AS treatment induced apoptosis, which was associated with DNA fragmentation, followed by a sequence of events, including intracellular ROS generation; mitochondrial dysfunction; Fas ligand activation; cytochrome c release; caspase-3, -8, -9, and PARP activation; and Bcl-2/Bax dysregulation. The results of the in vitro study suggested that AS-induced apoptosis in HL-60 cells was mediated by both the mitochondrial and death receptor pathways. Furthermore, we found that AS treatment was effective in delaying tumor incidence in HL-60 xenografted nude mice and reducing tumor burden.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report confirming the anti-tumor activity of this potentially beneficial mushroom against human promyelocytic leukemia.
authors.affiliation: Department of Cosmeceutics, College of Pharmacy, 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 Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Chuan-Chen
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Applied Chemistry, Chao Yang University of Technology, Taichung 41349, Taiwan.
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: K J Senthil
authors.initials: KJ
authors.lastname: Kumar
authors.affiliation: Department of Applied Chemistry, Chao Yang University of Technology, Taichung 41349, Taiwan.
authors.forename: Chee-Shan
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Institute of Nutrition, China Medical University, Taichung 40402, Taiwan.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 40402, Taiwan.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.affiliation: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Institute of Nutrition, 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 / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D055491:Antrodia / Q000302:isolation & purification; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents
keywords: Antrodia salmonea; Apoptosis; G(1) cell-cycle arrest; Human promyelocytic leukemia; Xenografted nude mice