Anticarcinogenic activities of sulforaphane are influenced by Nerve Growth Factor in human melanoma A375 cells

Food Chem Toxicol. 2018 Mar:113:154-161. doi: 10.1016/j.fct.2018.01.051. Epub 2018 Jan 31.

Abstract

Melanoma is a severe form of cancer, resistant to conventional therapies. According to in vitro studies, sulforaphane, a dietary component, has been considered a promising antineoplastic candidate. The present study analyzes the in vitro biological effects of sulforaphane in A375 melanoma cell line with or without the addition of Nerve Growth Factor. For the first time, our results show that a supplementation of Nerve Growth Factor partially reverses the sulforaphane-induced: i) inhibition of cell migration, ii) pro apoptotic changes in cell cycle and iii) modulation of active caspase-3. Furthermore, we report the sulforaphane-induced modulation in the expression of Nerve Growth Factor receptors TrKA and p75NTR, shifting their ratio from pro survival to pro apoptotic. In conclusion, the present study evidences that in vivo the antineoplastic effects of sulforaphane may be reduced by the contemporaneous presence of other biological elements such as Nerve Growth Factor and it contributes to a better definition of the real in vivo potentiality of sulforaphane as antineoplastic candidate.

Keywords: A375 cell line; Melanoma; NGF; Neurotrophins; Sulforaphane; TrKA; p75NTR.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Survival / physiology
  • Humans
  • Isothiocyanates / pharmacology*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Nerve Growth Factor / physiology*
  • Nerve Tissue Proteins / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, trkA / metabolism
  • Receptors, Nerve Growth Factor / metabolism
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Sulfoxides

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • NGFR protein, human
  • NTRK1 protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Sulfoxides
  • Nerve Growth Factor
  • Receptor, trkA
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3
  • sulforaphane