Exp Mol Med.  2008 Jun;40(3):313-319. 10.3858/emm.2008.40.3.313.

Effect of xanthohumol on melanogenesis in B16 melanoma cells

Affiliations
  • 1Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-756, Korea. jinwoo@chonbuk.ac.kr
  • 2Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan 570-749, Korea.
  • 3Department of Microbiology, College of Medicine, Inje University, Busan 614-735, Korea.
  • 4Department of Anatomy, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-756, Korea.
  • 5Department of Surgery, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-756, Korea.
  • 6Department of Dermatology, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-756, Korea.

Abstract

Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited alpha-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.

Keyword

cell differentiation; melanins; melanocytes; microphthalmia-associated transcription factor; monophenol monooxygenase; xanthohumol

MeSH Terms

1-Methyl-3-isobutylxanthine/pharmacology
Animals
Cell Line
Cell Survival/drug effects
Dose-Response Relationship, Drug
Down-Regulation
Drug Antagonism
Forskolin/pharmacology
*Humulus
Intramolecular Oxidoreductases/antagonists & inhibitors/biosynthesis
Melanins/antagonists & inhibitors/*biosynthesis
Melanocytes/*drug effects/*metabolism
Melanoma, Experimental
Membrane Glycoproteins/antagonists & inhibitors/biosynthesis
Mice
Microphthalmia-Associated Transcription Factor/antagonists & inhibitors
Monophenol Monooxygenase/antagonists & inhibitors/biosynthesis/genetics
Oxidoreductases/antagonists & inhibitors/biosynthesis
Propiophenones/*pharmacology
Signal Transduction/drug effects
alpha-MSH/metabolism
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