Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells
Author:
Rocha-Brito Karin J. P.12, Clerici Stefano Piatto1ORCID, Cordeiro Helon Guimarães1ORCID, Scotá Ferreira Amanda Petrina1, Barreto Fonseca Emanuella Maria13ORCID, Gonçalves Paola R.14, Abrantes Júlia Laura F.1, Milani Renato1, Massaro Renato Ramos5, Maria-Engler Silvya Stuchi5, Ferreira-Halder Carmen V.1ORCID
Affiliation:
1. Department of Biochemistry and Tissue Biology , Institute of Biology, University of Campinas , Campinas 13083-862 , SP , Brazil 2. Department of Medicine , Health Sciences Center, University Center of Maringá , Maringá , Paraná , Brazil 3. Federal Institute of Education, Science and Technology of São Paulo. São Roque , São Paulo , Brazil 4. Department of Health Sciences , Centro Universitário Norte do Espírito Santo, Universidade Federal do Espírito Santo , São Mateus , Espírito Santo , Brazil 5. Department of Clinical Chemistry and Toxicology , School of Pharmaceutical Sciences, University of São Paulo , São Paulo , Brazil
Abstract
Abstract
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.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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