Naringin suppresses the metabolism of A375 cells by inhibiting the phosphorylation of c-Src

Tumour Biol. 2016 Mar;37(3):3841-50. doi: 10.1007/s13277-015-4235-z. Epub 2015 Oct 17.

Abstract

Elevation of glycolysis, increase in lactic acid production, and enhancement of mitochondrial biogenesis are all the changes of energy metabolism of melanoma cells. Melanoma cells' metabolism and energy production networks play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Since the Warburg theory was put forward in the 1930s, more researchers focus on finding new ways for effectively eliminating cancer cells by targeting their energy metabolism. In this study, we found naringin has the inhibitory effects on the glucose metabolism of A375 cells, a melanoma cell line, in a concentration-dependent manner. We also found that naringin could significantly reduce the phosphorylation of c-Src. In summary, we demonstrated that naringin inhibits the malignant phenotype of A375 cells by suppressing c-Src and its downstream signaling pathway. More importantly, we provide the novel mechanism that, as a natural inhibitor of c-Src, naringin could be an effective candidate for the treatment of melanoma.

Keywords: A375 cells; Metabolism; Naringin; Signaling pathway; c-Src.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Blotting, Western
  • CSK Tyrosine-Protein Kinase
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Dose-Response Relationship, Drug
  • Energy Metabolism / drug effects*
  • Energy Metabolism / genetics
  • Flavanones / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucose / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism
  • Time Factors
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Carrier Proteins
  • Flavanones
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Thyroid Hormones
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Glucose
  • naringin