Effect of xanthohumol on melanogenesis in B16 melanoma cells.
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.
Koo
Jeung-Hyun
JH
Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Korea.
Kim
Hyoung Tae
HT
Yoon
Ha-Yong
HY
Kwon
Kang-Beom
KB
Choi
Il-Whan
IW
Jung
Sung Hoo
SH
Kim
Han-Uk
HU
Park
Byung-Hyun
BH
Park
Jin-Woo
JW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004336:Drug Antagonism; D005419:Flavonoids; D027582:Humulus; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008543:Melanins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D008546:Melanoma, Experimental; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011427:Propiophenones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism
D005419:Flavonoids; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D011427:Propiophenones; D005576:Colforsin; D000521:alpha-MSH; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C104536:xanthohumol; D015056:1-Methyl-3-isobutylxanthine