Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells.

Autor:	Rocha-Brito KJP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil.; Department of Medicine, Health Sciences Center, University Center of Maringá, Maringá, Paraná, Brazil., Clerici SP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil., Cordeiro HG; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil., Scotá Ferreira AP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil., Barreto Fonseca EM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil.; Federal Institute of Education, Science and Technology of São Paulo. São Roque, São Paulo, Brazil., Gonçalves PR; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil.; Department of Health Sciences, Centro Universitário Norte do Espírito Santo, Universidade Federal do Espírito Santo, São Mateus, Espírito Santo, Brazil., Abrantes JLF; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil., Milani R; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil., Massaro RR; Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Maria-Engler SS; Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Ferreira-Halder CV; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-862, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Biological chemistry [Biol Chem] 2021 Dec 03; Vol. 403 (3), pp. 293-303. Date of Electronic Publication: 2021 Dec 03 (Print Publication: 2022).
DOI:	10.1515/hsz-2021-0261
Abstrakt:	Melanoma is a type of skin cancer with low survival rates after it has metastasized. In order to find molecular differences that could represent targets of quercetin in anti-melanoma activity, we have chosen SKMEL-103 and SKMEL-28 melanoma cells and human melanocytes as models. Firstly, we observed that quercetin was able in reducing SKMEL-103 cell viability, but not in SKMEL-28. Besides that, quercetin treatment caused inhibition of AXL in both cell lines, but upregulation of PIM-1 in SKMEL-28 and downregulation in SKMEL-103. Moreover, HIF-1 alpha expression decreased in both cell lines. Interestingly, quercetin was more effective against SKMEL-103 than kinases inhibitors, such as Imatinib, Temsirolimus, U0126, and Erlotinib. Interestingly, we observed that while the levels of succinate dehydrogenase and voltage-dependent anion channel increased in SKMEL-103, both proteins were downregulated in SKMEL-28 after quercetin's treatment. Furthermore, AKT, AXL, PIM-1, ABL kinases were much more active and chaperones HSP90, HSP70 and GAPDH were highly expressed in SKMEL-103 cells in comparison with melanocytes. Our findings indicate, for the first time, that the efficacy of quercetin to kill melanoma cells depends on its ability in inhibiting tyrosine kinase and upregulating mitochondrial proteins, at least when SKMEL-103 and SKMEL-28 cells response were compared. (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu