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 language | English |
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Pages (from-to) | 340-349 |
Number of pages | 10 |
Journal | Biochimica et Biophysica Acta. Molecular Basis of Disease : BBA |
Volume | 1740 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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