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

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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
StatePublished - 2007

Fingerprint

Monophenol Monooxygenase
Quercetin
melanoma
quercetin
Melanoma
apoptosis
Apoptosis
glutathione transferase
cells
Glutathione Transferase
Antioxidant Response Elements
reactive oxygen species
Reactive Oxygen Species
quinones
cell free system
metabolism
response elements
oxidoreductases
drug resistance
Cell-Free System

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Food Science

Cite this

Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase. / Thangasamy, Thilakavathy; Sittadjody, Sivanandane; Lanza-Jacoby, Susan; Wachsberger, Phyllis R.; Limesand, Kirsten; Burd, Randy M.

In: Nutrition and Cancer, Vol. 59, No. 2, 2007, p. 258-268.

Research output: Contribution to journalArticle

Thangasamy, Thilakavathy ; Sittadjody, Sivanandane ; Lanza-Jacoby, Susan ; Wachsberger, Phyllis R. ; Limesand, Kirsten ; Burd, Randy M. / Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase. In: Nutrition and Cancer. 2007 ; Vol. 59, No. 2. pp. 258-268.
@article{11557795db224babbf97f7eb7d99151e,
title = "Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase",
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.",
author = "Thilakavathy Thangasamy and Sivanandane Sittadjody and Susan Lanza-Jacoby and Wachsberger, {Phyllis R.} and Kirsten Limesand and Burd, {Randy M}",
year = "2007",
language = "English (US)",
volume = "59",
pages = "258--268",
journal = "Nutrition and Cancer",
issn = "0163-5581",
publisher = "Routledge",
number = "2",

}

TY - JOUR

T1 - Quercetin selectively inhibits bioreduction and enhances apoptosis in melanoma cells that overexpress tyrosinase

AU - Thangasamy, Thilakavathy

AU - Sittadjody, Sivanandane

AU - Lanza-Jacoby, Susan

AU - Wachsberger, Phyllis R.

AU - Limesand, Kirsten

AU - Burd, Randy M

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=36849000866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36849000866&partnerID=8YFLogxK

M3 - Article

C2 - 18001220

AN - SCOPUS:36849000866

VL - 59

SP - 258

EP - 268

JO - Nutrition and Cancer

JF - Nutrition and Cancer

SN - 0163-5581

IS - 2

ER -