title: Bishydroquinone Renieramycin M Induces Apoptosis of Human Lung Cancer Cells Through a Mitochondria-dependent Pathway.
abstract: Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells.
  
  
  
  HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively. The key molecular markers of mitochondrial apoptosis pathway were determined by western blot analysis.
  
  
  
  HQ-RM exhibited stronger cytotoxicity than RM. HQ-RM reduced vitality of lung cancer cells in a dose-dependent manner. Nuclear staining assay indicated that apoptotic cell death was the main mechanism of toxicity caused by HQ-RM. Protein analysis revealed that HQ-RM-mediated apoptosis involved the increase of pro-apoptotic B-cell lymphoma 2 associated X (BAX) protein, and the decrease of anti-apoptosis myeloid cell leukemia 1 (MCL1) and B-cell lymphoma 2 (BCL2) proteins. Moreover, caspase-9 and -3 and Poly (ADP-ribose) polymerase (PARP) were dramatically cleaved in response to HQ-RM treatment.
  
  
  
  HQ-RM has highly potent anticancer activity, greater than its parental RM, and induces lung cancer cell apoptosis through a mitochondrial apoptosis caspase-dependent mechanism. This information benefits the development of this compound for cancer therapy.
authors.affiliation: Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.|Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Tatchakorn
authors.initials: T
authors.lastname: Pinkhien
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.|Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Arnatchai
authors.initials: A
authors.lastname: Maiuthed
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.|Center for Bioactive Natural Products from Marine Organisms and Endophytic Fungi, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Supakarn
authors.initials: S
authors.lastname: Chamni
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.|Center for Bioactive Natural Products from Marine Organisms and Endophytic Fungi, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Khanit
authors.initials: K
authors.lastname: Suwanborirux
authors.affiliation: Department of Pharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand pithi_chan@yahoo.com.|Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: D044005:Tetrahydroisoquinolines; C482478:renieramycin M
keywords: BCL2; Renieramycin M; apoptosis; bishydroquinone renieramycin M; lung cancer