Acta Pharmacologica Sinica 2006 November; 27 (11): 1467-1473; doi: 10.1111/j.1745-7254.2006.00435.x

Acta Pharmacologica Sinica 2006 November; 27 (11): 1467-1473; doi: 10.1111/j.1745-7254.2006.00435.x

Original Article

Stimulation of melanogenesis by scoparone in B16 melanoma cells

Jeong-yeh YANG², Jeung-hyun KOO³, Young-gil SONG³, Kang-beom KWON⁴, Ju-hyung LEE⁵,Hee-sook SOHN⁶, Byung-hyun PARK^3,7, Eun-chung JHEE², Jin-woo PARK^3,7,8

²Department of Biochemistry, Dental School, Chonbuk National University, Jeonju 561-756, Korea; ³Department of Biochemistry, Medical School, Chonbuk National University, Jeonju 561-756, Korea; ⁴Department of Physiology, School of Oriental Medicine, Won-Kwang University, Iksan 570-749, Korea;⁵Department of Preventive Medicine, Medical School, ⁶Department of Food Science and Human Nutrition, College of Home Economy, Chonbuk National University, Jeonju 561-756, Korea; ⁷Institute for Healthcare Technology Development, Chonbuk National University, Jeonju 561-756, Korea

Aim: The effect of coumarin derivatives on melanogenesis was investigated in B16 murine melanoma cells.

Methods: Melanin content and tyrosinase activity were analyzed spectrophotometrically. The expression of tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were measured either by reverse transcription-polymerase chain reaction (RT-PCR) or Western blot.

Results: Among the coumarin derivatives studied, scoparone (6,7-dimethoxycoumarin) was the most potent; the 6- or 7-methoxy group was found to be essential for the stimulation of melanogenesis. The melanin content was greatly increased by scoparone in a dose-dependent manner; there was no cytotoxicity at the effective concentrations. Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone. H-89, an inhibitor of protein kinase A (PKA), completely inhibited the scoparone-induced increase of melanogenesis and the tyrosinase protein.

Conclusion: These results suggest that scoparone-induced stimulation of melanogenesis is likely to occur at the transcriptional level of melanogenesis-related enzymes through PKA signaling.

Keywords: melanogenesis; scoparone (6,7-dimethoxy-coumarin); tyrosinase; tyrosinase-related proteins; protein kinase A

¹This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (the Center for Healthcare Technology Development, Chonbuk National University, Jeonju 561-756, Republic of Korea).

⁸Correspondence to Dr Jin-woo PARK.
Phn 82-63-270-3084.
Fax 82-63-274-9833.
E-mail jinwoo@chonbuk.ac.kr
Received 2006-03-14 Accepted 2006-06-16

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