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

Imiquimod Melanogenesis Reactive oxygen species

Journal

Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485

Informations de publication

Date de publication:
22 Dec 2023
Historique:
received: 06 10 2022
revised: 09 12 2023
accepted: 20 12 2023
medline: 8 1 2024
pubmed: 8 1 2024
entrez: 7 1 2024
Statut: aheadofprint

Résumé

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. To explore whether IMQ could induce melanogenesis in melanoma cells. 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. 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. Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

Sections du résumé

BACKGROUND 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 OBJECTIVE
To explore whether IMQ could induce melanogenesis in melanoma cells.
METHODS 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 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 CONCLUSIONS
Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

Identifiants

DOI: 10.1016/j.jdermsci.2023.12.005 PMID: 38185543
pubmed: 38185543
pii: S0923-1811(23)00268-2
doi: 10.1016/j.jdermsci.2023.12.005
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors have no conflict of interest to declare.

Auteurs

Zheng-Yi Li (ZY)

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Shu-Hao Chang (SH)

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Kuang-Ting Liu (KT)

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Pathology & Laboratory Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.

Alaina Edelie Wu (AE)

Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Chien-Sheng 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.

Shi-Wei Huang (SW)

Center for Cell Therapy and Translation Research, China Medical University Hospital, Taichung, Taiwan.

Mu-Chi 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.

Shih-Chung Wang (SC)

Division of Pediatric Hematology/Oncology, Changhua Christian Children Hospital, Changhua County, Taiwan.

Jun-Kai 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.

Yi-Ju 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.

Jeng-Jer 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.

Classifications MeSH