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

J Biol Chem. 2007 May 4;282(18):13468-76. doi: 10.1074/jbc.M610616200. Epub 2007 Mar 14.


Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables in human diets. They have broad biological activities including anti-mutagenesis 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-x(L) 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anthocyanins / chemistry
  • Anthocyanins / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / biosynthesis
  • Bcl-2-Like Protein 11
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Leukemic / drug effects
  • HL-60 Cells
  • Humans
  • Leukemia / drug therapy
  • Leukemia / metabolism*
  • Membrane Proteins / biosynthesis
  • Oxidative Stress / drug effects*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins / biosynthesis
  • Reactive Oxygen Species / metabolism
  • Rosaceae / chemistry
  • bcl-X Protein / biosynthesis


  • Anthocyanins
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Membrane Proteins
  • Plant Extracts
  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • bcl-X Protein
  • cyanidin 3-rutinoside