Metalloproteinases Suppression Driven by the Curcumin Analog DM-1 Modulates Invasion in BRAF-Resistant Melanomas

Autor(es)

de Souza, Nayane ^[1] ; de Oliveira, Erica Aparecida ^[1] ; Faiao-Flores, Fernanda ^[1] ; Pimenta, Luciana A. ^[2] ; Quincoces, Jose A. P. ^[3] ; Sampaio, Sandra C. ^[2] ; Maria-Engler, Silvya S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Clin Chem & Toxicol Dept, Skin Biol Grp, FCF USP, Sao Paulo - Brazil

^[2] Butantan Inst, Pathophysiol Lab, Sao Paulo - Brazil

^[3] Anhanguera Univ Sao Paulo, UNIAN, Lab Organ Synth, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 20, n. 9, p. 1038-1050, 2020.
• Citações Web of Science: 0

Resumo

Background: Melanoma is the most aggressive skin cancer, and BRAF (V600E) is the most frequent mutation that led to the development of BRAF inhibitors (BRAFi). However, patients treated with BRAFi usually present recidivism after 6-9 months. Curcumin is a turmeric substance, and it has been deeply investigated due to its anti-inflammatory and antitumoral effects. Still the low bioavailability and biodisponibility encouraged the investigation of different analogs. DM-1 is a curcumin analog and has shown an antitumoral impact in previous studies. Methods: Evaluated DM-1 stability and cytotoxic effects for BRAFi-sensitive and resistant melanomas, as well as the role in the metalloproteinases modulation. Results: DM-1 showed growth inhibitory potential for melanoma cells, demonstrated by reduction colony formation, migration and endothelial tube formation, and cell cycle arrest. Subtoxic doses were able to down-regulate important Metalloproteinases (MMPs I related to invasiveness, such as MMP-1, -2 and -9. Negative modulations of TEMP-2 and MMP-14 reduced MMP-2 and -9 activity; however, the reverse effect is seen when increased TIMP-2 and MMP-14 resulted in raised MMP-2. Conclusion: These findings provide essential details into the functional role of DM-1 in melanomas, encouraging further studies in the development of combinatorial treatments for melanomas. (AU)

• Processo FAPESP: 16/16554-3 - Genes emergentes na progressão e quimiorresistência do melanoma
• Beneficiário: Érica Aparecida de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/05172-4 - Impacto das proteínas da Transição epitélio-mesênquima em melanoma quimioresistente ao vemurabenibe
• Beneficiário: Fernanda Faião Flores
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/04926-6 - Melanoma e quimiorresistência: modelos in vitro e in silico para explorar alvos terapêuticos
• Beneficiário: Silvya Stuchi Maria-Engler
• Modalidade de apoio: Auxílio à Pesquisa - Temático