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

Biol Chem. 2021 Dec 3;403(3):293-303. doi: 10.1515/hsz-2021-0261. Print 2022 Feb 23.

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.

Keywords: melanoma; mitochondria; protein kinases; quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / pathology
  • Membrane Proteins / metabolism
  • Mitochondrial Proteins / metabolism
  • Proto-Oncogene Proteins c-pim-1 / metabolism
  • Proto-Oncogene Proteins c-pim-1 / pharmacology
  • Quercetin* / pharmacology
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / pharmacology
  • Succinate Dehydrogenase / metabolism
  • Tyrosine / pharmacology

Substances

  • Membrane Proteins
  • Mitochondrial Proteins
  • Tyrosine
  • Quercetin
  • Succinate Dehydrogenase
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-pim-1
  • GTP Phosphohydrolases
  • NRAS protein, human