Hinokitiol Inhibits Melanogenesis via AKT/mTOR Signaling in B16F10 Mouse Melanoma Cells

Int J Mol Sci. 2016 Feb 18;17(2):248. doi: 10.3390/ijms17020248.


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.

Keywords: autophagy; hinokitiol; melanogenesis; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Melanins / biosynthesis*
  • Melanoma, Experimental
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / metabolism
  • Monoterpenes / chemistry
  • Monoterpenes / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • Tropolone / analogs & derivatives*
  • Tropolone / chemistry
  • Tropolone / pharmacology


  • Antineoplastic Agents, Phytogenic
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Monoterpenes
  • Tropolone
  • Monophenol Monooxygenase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • beta-thujaplicin