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Isoquercitrin induces melanogenesis in B16F10 melanoma cells and zebrafish via the p38 and PKA/CREB signaling pathways: an experimental study

Year: 2025

Type: article

Abstract: BACKGROUND: Isoquercitrin (IQ), a flavonoid with anticancer, antioxidant, anti-inflammatory, and antiallergic properties, exhibits dual effects on B16F10 melanoma cells by suppressing cell viability and inducing hyperpigmentation. This study investigated the molecular mechanisms underlying IQ-induced melanogenesis in vitro and in vivo, highlighting the potential of IQ in the treatment of vitiligo. METHODS: B16F10 melanoma cells and zebrafish were treated with various IQ concentrations and melanogenesis was evaluated using western blotting, a tyrosinase activity assay, and microscopic observation. In addition, signaling pathway modulators and IQ were used to confirm the signaling pathways involved in IQ-induced melanogenesis. RESULTS: IQ treatment of B16F10 melanoma cells enhanced tyrosinase activity and upregulated melanogenesis-associated proteins, including microphthalmia-associated transcription factor and tyrosinase, via the p38 and protein kinase A (PKA)/cyclic AMP response element-binding protein (CREB) signaling pathways. Cotreatment with pathway-specific inhibitors (SB203580 for p38 and H89 for PKA/CREB) attenuated melanogenesis, whereas forskolin (a PKA/CREB activator) enhanced melanogenesis, confirming the involvement of these signaling pathways. In zebrafish, IQ treatment significantly increased melanophore production in the dorsal region following hypopigmentation induction with 1-phenyl-2-thiourea (PTU). Similar to that in B16F10 melanoma cells, SB203580 and H89 suppressed IQ-induced pigmentation, whereas forskolin enhanced it. CONCLUSION: These findings demonstrate that IQ promotes melanogenesis in vitro and in vivo through activation of the p38 and PKA/CREB signaling pathways, supporting its potential as a therapeutic agent for vitiligo.

Source: Journal of Yeungnam Medical Science

DOI: 10.12701/jyms.2025.42.69

Authors: Jun Ha Lee, Ye Sol Ko, Young Seok Eom, Song Ja Kim

Institution: Kongju National University

Language: English

Topic: melanin and skin pigmentation

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Research Foundation, Ministry of Education, National Research Foundation of Korea