Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase

Thilakavathy Thangasamy, Sivanandane Sittadjody, Susan Lanza-Jacoby, Phyllis R. Wachsberger, Kirsten H. Limesand, Randy Burd

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Tyrosinase is expressed in melanoma cells and catalyzes the formation of 3,3′,4′,5,7-pentahydroxyflavone (quercetin) into reactive quinone species and subsequent glutathionyl adducts. Therefore, we examined the effect of quercetin metabolism on the glutathione (GSH) bioreduction pathway and cell viability in DB-1 melanoma cells that express varying levels of tyrosinase (Tyr+). In a cell-free system, GSH was significantly decreased by quercetin, which coincided with the formation of glutathionyl adducts. In Tyr+ clones, quercetin decreased bioreduction capacity and increased reactive oxygen species (ROS) to a greater degree compared to control cells. The antioxidant/electrophile response element-induced enzymes, glutathione-S- transferase (GST), and nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 were expressed at high levels in Tyr+ cells and contributed to prooxidant quercetin metabolism. The basal level of ROS and apoptosis was higher in Tyr+ cells and were selectively increased after exposure to quercetin. The increase in apoptosis following quercetin exposure was p53/Bax mediated and correlated with a decrease in GST-driven bioreduction capacity and an increase in ROS. In conclusion, quercetin can selectively sensitize Tyr+ expressing melanoma cells to apoptosis and may serve as an adjuvant to chemotherapy by enhancing cell death and interfering with GST-mediated drug resistance.

Original languageEnglish (US)
Pages (from-to)258-268
Number of pages11
JournalNutrition and cancer
Volume59
Issue number2
DOIs
StatePublished - Jan 1 2007

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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