Staurosporine Drives Non‐Canonical Melanocyte Maturation by Coupling β‐Catenin Signaling to Actin‐Dependent Dendrite Remodeling

ABSTRACT

Skin pigmentation relies on the coordinated regulation of melanin production and dendritic morphology to ensure effective pigment distribution. While staurosporine is widely used as a pro‐apoptotic agent in malignant cells, its effects on normal human melanocytes remain poorly understood. Here, we investigated the effects of staurosporine on melanocyte biology and identified it as a potent inducer of non‐canonical melanocyte maturation at sub‐cytotoxic concentrations without stimulating melanocyte proliferation. In primary human melanocytes, staurosporine enhanced melanogenesis and promoted dendrite formation, elongation, and branching, resulting in acquisition of a mature melanocyte phenotype distinct from its apoptotic effects in melanoma cells. These phenotypic changes were accompanied by activation of β‐catenin signaling together with coordinated remodeling of Rho family protein expression and the actin cytoskeleton. Topical application of staurosporine increased physiological pigmentation in guinea pig skin without detectable inflammation or melanocyte proliferation. Furthermore, staurosporine accelerated repigmentation in a rhododendrol‐induced leukoderma model by promoting functional maturation of epidermal melanocytes and enhancing nuclear localization of β‐catenin. Collectively, our findings identify staurosporine as a non‐canonical regulator of melanocyte maturation and demonstrate that functional maturation, rather than proliferative expansion, is sufficient to enhance pigmentation under both physiological and depigmented conditions.