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In vitro induction of melanin synthesis and extrusion by tamoxifen
Author(s) -
Matamá T.,
Araújo R.,
Preto A.,
CavacoPaulo A.,
Gomes A. C.
Publication year - 2013
Publication title -
international journal of cosmetic science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.532
H-Index - 62
eISSN - 1468-2494
pISSN - 0142-5463
DOI - 10.1111/ics.12052
Subject(s) - tamoxifen , melanin , antiestrogen , catalase , cytotoxicity , melanocyte , pharmacology , in vitro , selective estrogen receptor modulator , chemistry , biology , endocrinology , medicine , biochemistry , enzyme , cancer research , melanoma , cancer , breast cancer
Synopsis Objectives Physical appearance has significant importance psychologically and socially, with skin and hair being of prime relevance. Effective ingredients that modulate melanin synthesis are of growing interest. Tamoxifen, a widely used selective oestrogen receptor modulator, SERM , was described occasionally in medical case reports as causing grey hair repigmentation. This work aimed to study, in vitro , the effect of tamoxifen and 4‐hydroxy‐tamoxifen, one of its most bioactive derivatives, on melanin production in human melanocytes. Methods Adult normal human epidermal melanocytes (NHEM) were treated with physiological concentrations of tamoxifen and 4‐hydroxy‐tamoxifen during 72 hours. Cytotoxicity was evaluated by lactate dehydrogenase (LDH) leakage. Total melanin was quantified by spectrophotometry, and cyclic adenosine monophosphate ( cAMP ) was determined by competitive ELISA. The relative mRNA levels of several genes involved in melanogenesis were investigated by real‐time PCR. Results Under the conditions used, the results showed that tamoxifen and 4‐hydroxy‐tamoxifen treatments, none of them toxic to NHEM, induced a time‐dependent increase in the amount of melanin released to the culture medium. cAMP , one of the major second messenger in signalling pathways important to melanogenesis, was decreased after treatment. The transcript levels of genes coding for catalase, premelanosome protein and melan‐A, directly related to skin and hair pigmentation, showed an increased tendency upon tamoxifen and 4‐hydroxy‐tamoxifen treatment. Induction of catalase gene expression in NHEM points towards a promelanogenic effect mediated by ROS . Conclusion According to the results, even in such a short treatment period, tamoxifen and 4‐hydroxy‐tamoxifen promoted melanin extrusion and they seem to act as melanogenesis stimulators at the molecular level. Our data suggest that SERM s might be a new tool for increasing melanogenesis and might be of great interest for topical formulations in cosmetic industry.

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