Implications of melanogenesis stimulation in B16-F10 cells on the ubiquitin-proteasome system

Autor(es)

Martins, Dainesy Santos ; Demasi, Marilene ; Bellan, Daniel de Lima ; Martinez, Glaucia Regina

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 787, p. 10-pg., 2025-11-01.

Resumo

The development of resistance by tumor cells is a challenge in cancer treatment; either in chemotherapy, immunotherapy and targeted therapy. Proteasome can be considered a promising therapeutic target, as it is considered the key to the ubiquitin-proteasome system (UPS), and is responsible for more than 80 % of cellular protein degradation. Considering that melanogenesis may be associated with melanoma resistance to treatments, this study aimed to investigate the response of melanoma cells with or without stimulation of melanogenesis against treatment with UPS inhibitors. We used murine melanoma cell line, B16-F10 with and without stimulation of melanogenesis. We investigated cell responses after treatments with UPS inhibitors BTZ or PYZD-4409. In melanogenesis-stimulated B16-F10, cells we observed resistance to the treatment with BTZ, with a decrease in the inhibition of proteasome, which attenuated the effects on cell viability and apoptosis. However, BTZ treatment in B16-F10 murine melanoma cells promoted proteasome inhibition, reduced percentage of viable cells and increased active caspase-3, causing cell death by apoptosis. In turn, in the inhibition of the ubiquitination process at E1 (first enzyme in the ubiquitination process) by the compound PYZD-4409, the stimulus of melanogenesis did not prevent the reduction in the percentage of metabolically active cells, decrease in percentage of adhered cells and induction of cell death by apoptosis. This study indicates that inhibition of protein ubiquitination would be an important alternative for the treatment of melanoma, however not by the inhibitors of the proteasome such as BTZ, especially in highly melanogenic tumors. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs