The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells.
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 microM) 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 (3)H-thymidine incorporation occurred with > or =10 microM kaempferol. One hundred micromolar kaempefrol increased the proportion of cells in G(2)-M phase, the proportion of cells with a sub-G(1) 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.
Bestwick
Charles S
CS
Phytochemical and Genomic Stability Group, Cellular Integrity Programme, Rowett Research Institute, Bucksburn, Aberdeen, UK. C.Bestwick@rowett.ac.uk
Milne
Lesley
L
Pirie
Lynn
L
Duthie
Susan J
SJ
D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology* / Q000633:toxicity; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D044949:Kaempferols; D017382:Reactive Oxygen Species; D014316:Tritium; C006552:kaempferol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013936:Thymidine