uercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cell

Author(s):Show less -

Rocha-Brito, Karin J. P. ^{[1, 2]} ; Clerici, Stefano Piatto ^[2] ; Cordeiro, Helon Guimaraes ^[2] ; Scota Ferreira, Amanda Petrina ^[2] ; Barreto Fonseca, Emanuella Maria ^{[3, 2]} ; Goncalves, Paola R. ^{[2, 4]} ; Abrantes, Julia Laura F. ^[2] ; Milani, Renato ^[2] ; Massaro, Renato Ramos ^[5] ; Maria-Engler, Silvya Stuchi ^[5] ; Ferreira-Halder, V, Carmen

Affiliation

^[1] Univ Ctr Maringa, Hlth Sci Ctr, Dept Med, Maringa, Parana - Brazil

^[2] V, Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, BR-13083862 Campinas - Brazil

^[3] Fed Inst Educ Sci & Technol Sao Paulo, Sao Roque, SP - Brazil

^[4] Univ Fed Espirito Santo, Ctr Univ Norte Espirito Santo, Dept Hlth Sci, Sao Mateus, ES - Brazil

^[5] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Biological Chemistry; v. 403, n. 3 DEC 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets
• Grantee: Silvya Stuchi Maria-Engler
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/03593-6 - Tumor-educated platelets and metastasis: relevance of LMWPTP and extracellular vesicles in Colorectal Cancer
• Grantee: Stefano Piatto Clerici
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/20412-7 - Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation
• Grantee: Carmen Veríssima Ferreira
• Support Opportunities: Research Projects - Thematic Grants