Cytotoxicity of dopamine-derived tetrahydroisoquinolines on melanoma cells

Federico De Marco, Marzia Perluigi, Maria Luisa Marcante, Raffaella Coccia, Cesira Foppoli, Carla Blarzino, Maria Anna Rosei

Research output: Contribution to journalArticlepeer-review

Abstract

Tetrahydroisoquinolines (TIQs) are endogenous alkaloid compounds detected in urine, central nervous system and some peripheral tissues in Mammalia. No data are at present available on TIQ levels in skin, although in vitro biochemical evidences indicate that they may undergo auto-oxidation with production of reactive oxygen species or may be enzymatically converted into melanin pigments. The effect of two catechol-bearing TIQs, salsolinol (SAL) and tetrahydropapaveroline (THP), on the viability of melanotic or amelanotic melanoma cell lines was investigated. Both SAL and THP were well tolerated up to roughly 30μM and became overtly toxic at higher concentrations, with SAL being better tolerated than THP. Intracellular activity of some antioxidant enzymes, tyrosinase and α-ketoglutarate dehydrogenase was also evaluated to assess the cell response to oxidative and metabolic challenge of TIQs treatment. Catalase and superoxide dismutase pre-treatment only partially prevented TIQs toxicity while a complete protection was obtained with N-acetylcysteine and GSH. TIQs were able to provoke upregulation of the scavenging enzymes catalase and DT-diaphorase and to determine a decrease of the α-ketoglutarate dehydrogenase activity. SAL and THP enhanced tyrosinase activity and melanin production, suggesting that they were indeed tyrosinase substrates leading to melanin formation. The results support the evidence that TIQs were toxic toward melanoma cells, leading to their death by necrosis. TIQs toxicity was likely due to increased oxidative stress by generation of reactive oxygen species and oxidative metabolites. Our study represents an intent to furnish an additional contribution for the comprehension of catechol cytotoxicity.

Original languageEnglish
Pages (from-to)1503-1512
Number of pages10
JournalBiochemical Pharmacology
Volume64
Issue number10
DOIs
Publication statusPublished - Nov 15 2002

Keywords

  • Cytotoxicity
  • Melanoma cells
  • Quinones
  • ROS
  • Tetrahydroisoquinolines

ASJC Scopus subject areas

  • Pharmacology

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