Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress

Rentian Feng, Hong Min Ni, Shiow Y. Wang, Irina L. Tourkova, Michael R. Shurin, Hisashi Harada, Xiao-Ming Yin

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables in human diets. They have broad biological activities including antimutagenesis and anticarcinogenesis, which are generally attributed to their antioxidant activities. We studied the effects and the mechanisms of the most common type of anthocyanins, cyanidin-3-rutinoside, in several leukemia and lymphoma cell lines. We found that cyanidin-3-rutinoside extracted and purified from the black raspberry cultivar Jewel induced apoptosis in HL-60 cells in a dose- and time-dependent manner. Paradoxically, this compound induced the accumulation of peroxides, which are involved in the induction of apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside treatment resulted in reactive oxygen species (ROS)-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway mediated by Bim. Down-regulation of Bim or overexpression of Bcl-2 or Bcl-xL considerably blocked apoptosis. Notably, cyanidin-3-rutinoside treatment did not lead to increased ROS accumulation in normal human peripheral blood mononuclear cells and had no cytotoxic effects on these cells. These results indicate that cyanidin-3-rutinoside has the potential to be used in leukemia therapy with the advantages of being widely available and selective against tumors.

Original languageEnglish (US)
Pages (from-to)13468-13476
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number18
DOIs
StatePublished - May 4 2007
Externally publishedYes

Fingerprint

Oxidative stress
Polyphenols
Oxidative Stress
Antioxidants
Anthocyanins
HL-60 Cells
Apoptosis
Reactive Oxygen Species
Leukemia
Peroxides
Vegetables
p38 Mitogen-Activated Protein Kinases
Cell death
Nutrition
Fruits
Bioactivity
Tumors
Fruit
Lymphoma
Blood Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. / Feng, Rentian; Ni, Hong Min; Wang, Shiow Y.; Tourkova, Irina L.; Shurin, Michael R.; Harada, Hisashi; Yin, Xiao-Ming.

In: Journal of Biological Chemistry, Vol. 282, No. 18, 04.05.2007, p. 13468-13476.

Research output: Contribution to journalArticle

Feng, Rentian ; Ni, Hong Min ; Wang, Shiow Y. ; Tourkova, Irina L. ; Shurin, Michael R. ; Harada, Hisashi ; Yin, Xiao-Ming. / Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 18. pp. 13468-13476.
@article{91439a6a522643e28047f2f02b7be63d,
title = "Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress",
abstract = "Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables in human diets. They have broad biological activities including antimutagenesis and anticarcinogenesis, which are generally attributed to their antioxidant activities. We studied the effects and the mechanisms of the most common type of anthocyanins, cyanidin-3-rutinoside, in several leukemia and lymphoma cell lines. We found that cyanidin-3-rutinoside extracted and purified from the black raspberry cultivar Jewel induced apoptosis in HL-60 cells in a dose- and time-dependent manner. Paradoxically, this compound induced the accumulation of peroxides, which are involved in the induction of apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside treatment resulted in reactive oxygen species (ROS)-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway mediated by Bim. Down-regulation of Bim or overexpression of Bcl-2 or Bcl-xL considerably blocked apoptosis. Notably, cyanidin-3-rutinoside treatment did not lead to increased ROS accumulation in normal human peripheral blood mononuclear cells and had no cytotoxic effects on these cells. These results indicate that cyanidin-3-rutinoside has the potential to be used in leukemia therapy with the advantages of being widely available and selective against tumors.",
author = "Rentian Feng and Ni, {Hong Min} and Wang, {Shiow Y.} and Tourkova, {Irina L.} and Shurin, {Michael R.} and Hisashi Harada and Xiao-Ming Yin",
year = "2007",
month = "5",
day = "4",
doi = "10.1074/jbc.M610616200",
language = "English (US)",
volume = "282",
pages = "13468--13476",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress

AU - Feng, Rentian

AU - Ni, Hong Min

AU - Wang, Shiow Y.

AU - Tourkova, Irina L.

AU - Shurin, Michael R.

AU - Harada, Hisashi

AU - Yin, Xiao-Ming

PY - 2007/5/4

Y1 - 2007/5/4

N2 - Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables in human diets. They have broad biological activities including antimutagenesis and anticarcinogenesis, which are generally attributed to their antioxidant activities. We studied the effects and the mechanisms of the most common type of anthocyanins, cyanidin-3-rutinoside, in several leukemia and lymphoma cell lines. We found that cyanidin-3-rutinoside extracted and purified from the black raspberry cultivar Jewel induced apoptosis in HL-60 cells in a dose- and time-dependent manner. Paradoxically, this compound induced the accumulation of peroxides, which are involved in the induction of apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside treatment resulted in reactive oxygen species (ROS)-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway mediated by Bim. Down-regulation of Bim or overexpression of Bcl-2 or Bcl-xL considerably blocked apoptosis. Notably, cyanidin-3-rutinoside treatment did not lead to increased ROS accumulation in normal human peripheral blood mononuclear cells and had no cytotoxic effects on these cells. These results indicate that cyanidin-3-rutinoside has the potential to be used in leukemia therapy with the advantages of being widely available and selective against tumors.

AB - Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables in human diets. They have broad biological activities including antimutagenesis and anticarcinogenesis, which are generally attributed to their antioxidant activities. We studied the effects and the mechanisms of the most common type of anthocyanins, cyanidin-3-rutinoside, in several leukemia and lymphoma cell lines. We found that cyanidin-3-rutinoside extracted and purified from the black raspberry cultivar Jewel induced apoptosis in HL-60 cells in a dose- and time-dependent manner. Paradoxically, this compound induced the accumulation of peroxides, which are involved in the induction of apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside treatment resulted in reactive oxygen species (ROS)-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway mediated by Bim. Down-regulation of Bim or overexpression of Bcl-2 or Bcl-xL considerably blocked apoptosis. Notably, cyanidin-3-rutinoside treatment did not lead to increased ROS accumulation in normal human peripheral blood mononuclear cells and had no cytotoxic effects on these cells. These results indicate that cyanidin-3-rutinoside has the potential to be used in leukemia therapy with the advantages of being widely available and selective against tumors.

UR - http://www.scopus.com/inward/record.url?scp=34250324303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250324303&partnerID=8YFLogxK

U2 - 10.1074/jbc.M610616200

DO - 10.1074/jbc.M610616200

M3 - Article

VL - 282

SP - 13468

EP - 13476

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -