Tunlametinib Suppresses Melanogenesis Induces Cell Cycle Arrest and Apoptosis in Giant Congenital Melanocytic Nevus Cells.
- 1Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Abstract
Background/Objectives: Giant congenital melanocytic nevus (GCMN) is a rare developmental disorder arising from abnormal proliferation and differentiation of neural crest-derived melanocytes. It poses substantial clinical challenges due to cosmetic disfigurement, malignant potential, and the limited efficacy of current treatments. This study aimed to investigate the therapeutic effects and underlying molecular mechanisms of tunlametinib (HL-085), a novel selective MEK1/2 inhibitor, in GCMN. Methods: Primary GCMN cells and human GCMN explants were isolated, cultured, and validated to establish in vitro cellular and explant models. Following tunlametinib treatment, global transcriptional changes were analyzed using bulk RNA sequencing. Melanogenesis was assessed via Fontana-Masson staining, Western blotting, and immunofluorescence. Cell viability, apoptosis, and cell cycle distribution were evaluated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blotting for apoptosis- and cell cycle-related proteins. Results: Tunlametinib treatment significantly suppressed melanogenesis in GCMN cells and explant tissues at the phenotypic, histological, and protein levels, and reduced cell viability in a concentration-dependent manner. Transcriptomic analysis revealed marked alterations in gene expression profiles following treatment, with prominent changes in apoptosis- and cell cycle-related genes. Subsequent cellular assays and tissue staining confirmed that tunlametinib significantly increased early apoptosis and induced G1/S cell cycle arrest. Conclusions: Collectively, our findings demonstrate that tunlametinib inhibits proliferation and melanin production in GCMN cells by modulating the RAS-ERK pathway, providing a theoretical basis for its use as a targeted therapeutic strategy for GCMN.
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BibTeX
@article{guan2026tunlametinib,
title = {{Tunlametinib Suppresses Melanogenesis Induces Cell Cycle Arrest and Apoptosis in Giant Congenital Melanocytic Nevus Cells.}},
author = {Jin-Ye Guan and Zhuo Chen and Wen-Shang Liu and Jia-Long Xu and Zhi-Yu Zhou and Lina Song and Dan Deng},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193166},
url = {https://europepmc.org/article/MED/42882860},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tunlametinib Suppresses Melanogenesis Induces Cell Cycle Arrest and Apoptosis in Giant Congenital Melanocytic Nevus Cells.
AU - Jin-Ye Guan
AU - Zhuo Chen
AU - Wen-Shang Liu
AU - Jia-Long Xu
AU - Zhi-Yu Zhou
AU - Lina Song
AU - Dan Deng
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18193166
UR - https://europepmc.org/article/MED/42882860
AB - Background/Objectives: Giant congenital melanocytic nevus (GCMN) is a rare developmental disorder arising from abnormal proliferation and differentiation of neural crest-derived melanocytes. It poses substantial clinical challenges due to cosmetic disfigurement, malignant potential, and the limited efficacy of current treatments. This study aimed to investigate the therapeutic effects and underlying molecular mechanisms of tunlametinib (HL-085), a novel selective MEK1/2 inhibitor, in GCMN. Methods: Primary GCMN cells and human GCMN explants were isolated, cultured, and validated to establish in vitro cellular and explant models. Following tunlametinib treatment, global transcriptional changes were analyzed using bulk RNA sequencing. Melanogenesis was assessed via Fontana-Masson staining, Western blotting, and immunofluorescence. Cell viability, apoptosis, and cell cycle distribution were evaluated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blotting for apoptosis- and cell cycle-related proteins. Results: Tunlametinib treatment significantly suppressed melanogenesis in GCMN cells and explant tissues at the phenotypic, histological, and protein levels, and reduced cell viability in a concentration-dependent manner. Transcriptomic analysis revealed marked alterations in gene expression profiles following treatment, with prominent changes in apoptosis- and cell cycle-related genes. Subsequent cellular assays and tissue staining confirmed that tunlametinib significantly increased early apoptosis and induced G1/S cell cycle arrest. Conclusions: Collectively, our findings demonstrate that tunlametinib inhibits proliferation and melanin production in GCMN cells by modulating the RAS-ERK pathway, providing a theoretical basis for its use as a targeted therapeutic strategy for GCMN.
SN - 2072-6694
ER -