Effect of pyrroloquinoline quinone (PQQ) on melanogenic protein expression in murine B16 melanoma

J Dermatol Sci. 2009 Feb;53(2):140-5. doi: 10.1016/j.jdermsci.2008.08.017. Epub 2008 Nov 17.

Abstract

Background: Increased production and accumulation of melanin leads to various hyperpigmentation disorders. Melanin synthesis is regulated by melanogenic proteins such as tyrosinase, tyrosinase-related protein (TRP)-1 and -2, and their transcription factors.

Objective: In this study, we assessed the effects of PQQ on melanogenic protein expression of murine B16 melanoma cells.

Methods: We assessed melanin production of PQQ-treated B16 melanoma cells. Furthermore, we investigated the effect of PQQ on the activity of melanogenic enzymes and their expression using Western blot and semi-quantitative RT-PCR analyses.

Results: In the present study, PQQ inhibited melanin synthesis in cultured melanoma cells stimulated by either alpha-melanocyte stimulating hormone (alpha-MSH) or 3-isobutyl-1-methylxanthine (IBMX). To elucidate the mechanism of the effect of PQQ on melanogenesis, we performed Western blotting for melanogenic proteins, such as tyrosinase, TRP-1, and TRP-2. PQQ inhibited tyrosinase expression, however, it did not inhibit TRP-2 expression. Used as the stimulant for melanogenesis, both alpha-MSH and IBMX gave the same results for melanogenic protein expression. Semi-quantitative RT-PCR analysis showed that the depigmentation effect of PQQ might be due to the inhibition of tyrosinase gene transcription but not the inhibition of microphthalmia-associated transcription factor (Mitf).

Conclusion: This report indicates that PQQ is a possible anti-melanogenic agent and might be effective against hyperpigmentation disorders.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Intramolecular Oxidoreductases / metabolism
  • Melanins / biosynthesis*
  • Melanoma, Experimental / enzymology*
  • Melanoma, Experimental / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism*
  • Oxidoreductases / metabolism
  • PQQ Cofactor / pharmacology*
  • Pigmentation / drug effects*
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects
  • alpha-MSH / metabolism

Substances

  • Melanins
  • Membrane Glycoproteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • RNA, Messenger
  • alpha-MSH
  • PQQ Cofactor
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • Monophenol Monooxygenase
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
  • 1-Methyl-3-isobutylxanthine