Sorafenib induces pigmentation via the regulation of β-catenin signalling pathway in melanoma cells.

Tytuł:: Sorafenib induces pigmentation via the regulation of β-catenin signalling pathway in melanoma cells.
Autorzy:: Kim KI; Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.; Department of Medical Science, School of Medicine, Chungnam National University, Daejeon, Korea.; Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Korea.
Jung KE; Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
Shin YB; Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Korea.
Kim CD; Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.; Department of Medical Science, School of Medicine, Chungnam National University, Daejeon, Korea.
Yoon TJ; Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Korea.
Źródło:: Experimental dermatology [Exp Dermatol] 2022 Jan; Vol. 31 (1), pp. 57-63. Date of Electronic Publication: 2020 Jul 08.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Copenhagen : Munksgaard, c1992-
MeSH Terms:: Antineoplastic Agents/*pharmacology
Melanoma/*pathology
Pigmentation/*drug effects
Skin Neoplasms/*pathology
Sorafenib/*pharmacology
beta Catenin/*metabolism
Antineoplastic Agents/metabolism ; Cell Line, Tumor ; Humans ; Signal Transduction/drug effects ; Sorafenib/metabolism
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Contributed Indexing:: Keywords: GSK3β; pigmentation; sorafenib; β-catenin
Substance Nomenclature:: 0 (Antineoplastic Agents)
0 (beta Catenin)
9ZOQ3TZI87 (Sorafenib)
Entry Date(s):: Date Created: 20200512 Date Completed: 20220329 Latest Revision: 20220329
Update Code:: 20240105
DOI:: 10.1111/exd.14112
PMID:: 32391926
: Czasopismo naukowe

Pełny tekst

We conducted large-scale screening test on drugs that were already approved for other diseases to find pigmentation-modulating agents. Among drugs with potential for pigmentation control, we selected sorafenib and further investigated the effect on pigmentation using HM3KO melanoma cells. As a result of treating melanoma cells with sorafenib, pigmentation was promoted in terms of melanin content and tyrosinase activity. Sorafenib increased mRNA and protein levels of pigmentation-related genes such as MITF, tyrosinase and TRP1. To uncover the action mechanism, we investigated the effect of sorafenib on the intracellular signalling pathways. Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. In addition, sorafenib significantly increased the level of active β-catenin, together with activation of β-catenin signalling. Mechanistic study revealed that sorafenib decreased phosphorylation of serine 9 (S9) of GSK3β, while it increased phosphorylation of tyrosine 216 (Y216) of GSK3β. These results suggest that sorafenib activates the β-catenin signalling through the regulation of GSK3β phosphorylation, thereby affecting the pigmentation process.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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