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

Autor:	de Souza N; Skin Biology Group, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of Sao Paulo, FCF/USP, Brazil., de Oliveira ÉA; Skin Biology Group, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of Sao Paulo, FCF/USP, Brazil., Faião-Flores F; Skin Biology Group, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of Sao Paulo, FCF/USP, Brazil., Pimenta LA; Butantan Institute, Pathophysiology Laboratory, Sao Paulo, Brazil., Quincoces JAP; Laboratory of Organic Synthesis, Anhanguera University of São Paulo, UNIAN, Sao Paulo, Brazil., Sampaio SC; Butantan Institute, Pathophysiology Laboratory, Sao Paulo, Brazil., Maria-Engler SS; Skin Biology Group, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of Sao Paulo, FCF/USP, Brazil.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2020; Vol. 20 (9), pp. 1038-1050.
DOI:	10.2174/1871520620666200218111422
Abstrakt:	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 of colony formation, migration and endothelial tube formation, and cell cycle arrest. Subtoxic doses were able to downregulate important Metalloproteinases (MMPs) related to invasiveness, such as MMP-1, -2 and -9. Negative modulations of TIMP-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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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