The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells

Charles Bestwick, Lesley Milne, Lynn Peters Pirie, Susan Joyce Duthie

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25 Citations (Scopus)

Abstract

Flavonoids may be a principal contributor to the cancer preventative activity of fruit- and vegetable-rich diets and there is interest in their use as dietary supplements. However, there is potential conflict between the cytoprotective and cytotoxic activities of flavonoids, and their efficacy as anti-cancer agents is unresolved. Here, the integrity and survival of HL-60 promyelocytic leukaemia cells following short-term (90 min) exposure to the dietary abundant flavonoid kaempferol (1-100 mu M) is reported. Supplementation initially decreased reactive oxygen levels but, paradoxically, a dose-dependent increase in single-strand DNA breakage occurred. However, there was no increase in oxidised DNA purines or membrane damage. Following a 24-h recovery period in non-kaempferol supplemented media, DNA single-strand breakage had declined and kaempferol exposed and control cultures possessed similar reactive oxygen levels. A reduction in H-3-thymidine incorporation occurred with >= 10 mu M kaempferol. One hundred micromolar kaempefrol increased the proportion of cells in G(2)-M phase, the proportion of cells with a sub-G, DNA content and enhanced 'active' caspase-3 expression but only induced a loss of mitochondrial membrane potential within a minority of cells. The relevance of induced DNA damage within a non-overtly oxidatively stressed environment to the disease preventative and therapeutic use of kaempferol is discussed. (c) 2004 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalBiochimica et Biophysica Acta. Molecular Basis of Disease : BBA
Volume1740
Issue number3
DOIs
Publication statusPublished - 10 Jun 2005

Keywords

  • cell cycle
  • DNA damage
  • flavonoid
  • HL-60
  • kaempferol
  • oxidative stress
  • CACO-2 INTESTINAL-CELLS
  • OXIDATIVE DNA-DAMAGE
  • LIPID-PEROXIDATION
  • DIETARY FLAVONOIDS
  • URACIL MISINCORPORATION
  • DISTINCT MECHANISMS
  • INDUCED APOPTOSIS
  • STRAND BREAKS
  • HEART-DISEASE
  • FREE-RADICALS
  • kaempferol
  • oxidative stress

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