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A regulator of ubiquitin–proteasome activity, 2‐hexyldecanol, suppresses melanin synthesis and the appearance of facial hyperpigmented spots
Author(s) -
Hakozaki T.,
Laughlin T.,
Zhao S.,
Wang J.,
Deng D.,
JewellMotz E.,
Elstun L.
Publication year - 2013
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.12364
Subject(s) - melanin , mg132 , human skin , proteasome inhibitor , proteasome , downregulation and upregulation , melanocyte , hyperpigmentation , melanosome , melanoma , biology , microbiology and biotechnology , cancer research , biochemistry , genetics , gene
Summary Background 2‐Hexyldecanol has long been used in skin‐care products, but has not previously been reported as an active ingredient for skin benefits. Objectives To evaluate 2‐hexyldecanol in in vitro and ex vivo systems and, if found to be active, progress it to topical clinical testing to determine effects on pigmentation in skin. Methods 2‐Hexyldecanol was tested in melanocyte cell culture systems ( B 16 mouse melanoma cells and normal human melanocytes) for its effect on proteolytic activity and melanin production, in the absence and presence of the proteasome‐specific inhibitor, MG 132. It was further tested in a human skin explant model for its effect on melanin production. Lastly, topically applied 2‐hexyldecanol was evaluated for its effect on the appearance of facial pigmentation in an 8‐week, randomized, double‐blind, vehicle‐controlled, split‐face incomplete block design study in C hinese women. Results In submerged cell culture, 2‐hexyldecanol upregulated proteolytic activity and decreased melanin synthesis. These effects were antagonized by the proteasome‐specific inhibitor MG 132. MG 132, tested in the absence of 2‐hexyldecanol, increased melanin production. In a human skin explant model, topical 2‐hexyldecanol suppressed the production of melanin vs. a vehicle control. In a human clinical study in C hinese women ( n = 110 observations per test material), a 2‐hexyldecanol‐containing formulation significantly reduced the appearance of facial hyperpigmented spots vs. its control. Conclusions These data indicate that regulation of proteasome activity is a viable target for control of melanin production, that 2‐hexyldecanol upregulates proteasomal activity in melanocytes, and that topical 2‐hexyldecanol reduces the appearance of hyperpigmentation.