title: Hinokitiol induces autophagy in murine breast and colorectal cancer cells.
abstract: Hinokitiol is found in the heartwood of cupressaceous plants and possesses several biological activities. Hinokitiol may play an important role in anti-inflammation and antioxidant processes, making it potentially useful in therapies for inflammatory-mediated disease. Previously, the suppression of tumor growth by hinokitiol has been shown to occur through apoptosis. Programmed cell death can also occur through autophagy, but the mechanism of hinokitiol-induced autophagy in tumor cells is poorly defined. We used an autophagy inhibitor (3-methyladenine) to demonstrate that hinokitiol can induce cell death via an autophagic pathway. Further, we suggest that hinokitiol induces autophagy in a dose-dependent manner. Markers of autophagy were increased after tumor cells were treated with hinokitiol. In addition, immunoblotting revealed that the levels of phosphoprotein kinase B (P-AKT), phosphomammalian target of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70S6K) in tumor cells were decreased after hinokitiol treatment. In conclusion, our results indicate that hinokitiol induces the autophagic signaling pathway via downregulation of the AKT/mTOR pathway. Therefore, our findings show that hinokitiol may control tumor growth by inducing autophagic signaling.
authors.affiliation: Department of Environmental Engineering and Science, Feng Chia University, Taichung, Taiwan.
authors.forename: Wei-Kuang
authors.initials: WK
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Lin
authors.affiliation: Department of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Liu
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Tom Yu-Tung
authors.initials: TY
authors.lastname: Li
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Kuo
authors.affiliation: Department of Nursing, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Jeng-Long
authors.initials: JL
authors.lastname: Hsieh
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D039821:Monoterpenes / Q000627:therapeutic use / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014334:Tropolone / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D039821:Monoterpenes; D014334:Tropolone; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C009479:beta-thujaplicin
keywords: antitumor; autophagy; hinokitiol