Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45

Minjeong Kim, Heung Soo Baek, Miri Lee, Hyeonji Park, Song Seok Shin, Dal Woong Choi, Kyung Min Lim

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma.

Original languageEnglish
Pages (from-to)339-346
Number of pages8
JournalToxicology in Vitro
StatePublished - 1 Apr 2016

Bibliographical note

Funding Information:
This work is supported by the National Research Foundation of Korea (Grant No. NRF-2015R1D1A1A01057931 ) and by the Ministry of Health & Welfare, Republic of Korea (Grant No. HN15C0102 ).

Publisher Copyright:
© 2016 Elsevier Ltd.


  • B16F10 cell
  • GADD45
  • Human melanocytes
  • Raspberry ketone
  • Rhododenol


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