title: Ferruginol inhibits non-small cell lung cancer growth by inducing caspase-associated apoptosis.
abstract: OBJECTIVE
  The anti-lung cancer effect of Cryptomeria japonica leaf extractive and its active phytocompound was evaluated using in vitro and in vivo assays.
  
  
  METHODS
  The anti-lung cancer mechanism was investigated using flow cytometry and western blot analyses, and the antitumor activity was evaluated in a xenograft animal model.
  
  
  RESULTS
  MTT assay indicated that the cytotoxic effects of ferruginol in A549 and CL1-5 cells were dose-dependent. According to the results of cell cycle and annexin V/PI analyses, the sub-G1 population and annexin V binding in the 2 cell lines were increased after ferruginol treatment. The results of western blot analyses revealed that the cleaved forms of caspase 3, 8, 9, and poly(ADP-ribose) polymerase were activated after ferruginol treatment in A549 and CL1-5 cells. Moreover, the expression of the anti-apoptotic protein Bcl-2 was decreased, while the expression of the pro-apoptotic protein Bax was elevated, after ferruginol treatment in both lung cancer cell lines. These results indicated that ferruginol acted via a caspase-dependent mitochondrial apoptotic pathway in the 2 cell lines. Intraperitoneal administration of ferruginol significantly suppressed the growth of subcutaneous CL1-5 xenografts.
  
  
  CONCLUSIONS
  The findings of the present study provided insight into the molecular mechanisms underlying ferruginol-induced apoptosis in non-small cell lung cancer (NSCLC) cells, indicating that this compound may be a potential candidate drug for anti-NSCLC.
authors.affiliation: National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shang-Tse
authors.initials: ST
authors.lastname: Ho
authors.affiliation: National Chung Hsing University, Taichung, Taiwan.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Tung
authors.affiliation: China Medical University, Taichung, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.affiliation: National Chung Hsing University, Taichung, Taiwan eric@nchu.edu.tw lincc@nuhu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Wu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020169:Caspases / Q000378:metabolism*; D032485:Cryptomeria / Q000737:chemistry*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008517:Phytotherapy; D018515:Plant Leaves / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C431074:ferruginol; D020169:Caspases
keywords: Cryptomeria japonica; NSCLC; apoptosis; caspase; ferruginol; lung cancer; phytocompound