α-MSH Induces Intracellular ROS Generation in Melanoma Cells through NADPH Oxidase-1/4 Activation
10.4062/biomolther.2025.258
- Author:
Kyuri KIM
1
;
Jihyun YOON
;
Hye Yeon KIM
;
Kyung-Min LIM
Author Information
1. College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2026;34(3):709-721
- CountryRepublic of Korea
- Language:English
-
Abstract:
α-Melanocyte-stimulating hormone (α-MSH) is a key physiological inducer of melanogenesis and melanocyte activation. Reactive oxygen species (ROS) function as secondary messengers in intracellular signaling pathways that regulate α-MSH-mediated melanogenesis. However, the mechanism by which α-MSH induces ROS generation in melanocytes remains incompletely understood. Here, we investigated the sources and regulatory mechanisms of α-MSH-induced ROS in murine B16F10 and human MNT-1 melanoma cells. Confocal microscopy revealed that α-MSH predominantly stimulated cytosolic rather than mitochondrial ROS generation. Western blot analysis showed that α-MSH upregulated the expression of NADPH oxidases NOX1 and NOX4 at early time points, key enzymes involved in cytosolic ROS production. Pharmacological inhibition of NOX1/4 significantly reduced α-MSH-induced ROS levels and melanin content, accompanied by decreased phosphorylation of MITF, a melanogenic transcription factor. These findings indicate that α-MSH is a key physiological inducer of melanogenesis and melanocyte-related signaling in melanoma cells. Our study highlights NOX4, together with NOX1, as potential targets for anti-pigmentation strategies.
