title: Hinokitiol Inhibits Melanogenesis via AKT/mTOR Signaling in B16F10 Mouse Melanoma Cells.
abstract: H inokitiol purified from the heartwood of cupressaceous plants has had various biological functions of cell differentiation and growth. Hinokitiol has been demonstrated as having an important role in anti-inflammation and anti-bacteria effect, suggesting that it is potentially useful in therapies for hyperpigmentation. Previously, hinokitiol inhibited the production of melanin by inhibiting tyrosinase activity. The autophagic signaling pathway can induce hypopigmentation. This study is warranted to investigate the mechanism of hinokitiol-induced hypopigmentation through autophagy in B16F10 melanoma cells. The melanin contents and expression of microthphalmia associated transcription factor (MITF) and tyrosinase were inhibited by treatment with hinokitiol. Moreover, the phosphorylation of the protein express levels of phospho-protein kinase B (P-AKT) and phospho-mammalian targets of rapamycin (P-mTOR) were reduced after hinokitiol treatment. In addition, the microtubule associated protein 1 light chain 3 (LC3) -II and beclin 1 (autophagic markers) were increased after the B16F10 cell was treated with hinokitiol. Meanwhile, hinokitiol decreased cellular melanin contents in a dose-dependent manner. These findings establish that hinokitiol inhibited melanogenesis through the AKT/mTOR signaling pathway.
authors.affiliation: Division of Nephrology, Department of Medicine, Taoyuan General Hospital, Taoyuan 330, Taiwan. tsaoyutzu@gmail.com.|Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan. tsaoyutzu@gmail.com.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tsao
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan. u103000425@cmu.edu.tw.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 404, Taiwan. u104082801@cmu.edu.tw.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 404, Taiwan. s225701048@gmail.com.
authors.forename: Yu-Chiang
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Environmental Engineering and Science, Feng Chia University, Taichung 40407, Taiwan. winton05@hotmail.com.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chiang
authors.affiliation: Department of Environmental Engineering and Science, Feng Chia University, Taichung 40407, Taiwan. wkwang@fcu.edu.tw.
authors.forename: Wei-Kuang
authors.initials: WK
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 404, Taiwan. m5210115@gmail.com.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan. chlee@mail.cmu.edu.tw.|Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 404, Taiwan. chlee@mail.cmu.edu.tw.|Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. chlee@mail.cmu.edu.tw.
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D039821:Monoterpenes; D014334:Tropolone; D014442:Monophenol Monooxygenase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C009479:beta-thujaplicin
keywords: autophagy; hinokitiol; melanogenesis; melanoma