Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway.

Autor: Li ZY; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan., Chang SH; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan., Liu KT; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Pathology & Laboratory Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan., Wu AE; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan., Hsu CS; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan., Huang SW; Center for Cell Therapy and Translation Research, China Medical University Hospital, Taichung, Taiwan., Chung MC; Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; PhD Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan., Wang SC; Division of Pediatric Hematology/Oncology, Changhua Christian Children Hospital, Changhua County, Taiwan., Kao JK; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan., Chen YJ; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan., Shieh JJ; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan. Electronic address: shiehjj@dragon.nchu.edu.tw.
Jazyk: angličtina
Zdroj: Journal of dermatological science [J Dermatol Sci] 2024 Jan; Vol. 113 (1), pp. 18-25. Date of Electronic Publication: 2023 Dec 22.
DOI: 10.1016/j.jdermsci.2023.12.005
Abstrakt: Background: Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity.
Objective: To explore whether IMQ could induce melanogenesis in melanoma cells.
Methods: The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not.
Results: We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity.
Conclusions: Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.
Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare.
(Copyright © 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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