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Research: CHAU and colleagues, I
Listed in Issue 35
Abstract
CHAU and colleagues, Institute of Anatomy, School of Life Sciences, National Yang-Ming University, Taiwan report that beta-lapachone, a new topoisomerase inhibitor (enzymes which regulate DNA supercoiling and which can introduce transient break-and-splice into DNA during replication), has been found to induce apoptosis (suicide) in human cancer cells .
Background
Methodology
Human leukaemia HL-60 cells were treated with 1 microM beta-lapachone.
Results
There was a dramatic elevation of hydrogen peroxide (H2O2) following beta-lapachone treatment and this increase was effectively inhibited by treatment with the antioxidant N-acetyl-L-cysteine (NAC), ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E). NAC strongly prevented beta-lapachone-induced apoptotic characteristics including DNA fragmentation and apoptotic morphology. However, treatment of HL-60 cells with another topoisomerase inhibitor camtothecin (CPT) did not induce H2O2 production compared to untreated cells. Cancer cells lines K562, MCF-7 and SW620 contained high levels of intracellular glutathione (GSH) were not elevated in H2O2 and were resistant to apoptosis following treatment with beta-lapachone. However, cancer cell lines such as HL-60, U937 and Molt-4, having lower levels of GSH were readily increased with H2O2 and conferred resistance to beta-lapachone-induced cell death. Beta-Lapachone at concentrations as low as 0.25 microM induced HL-60 cells to undergo monocytic differentiation, which was suppressed by NAC.
Conclusion
These data suggest that intracellular H2O2 generation plays a crucial role in beta-lapachone-induced cell death and differentiation.
References
Chau YP et al. Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone-induced apoptosis and differentiation in human leukemia cells. Free Radic Biol Med 24(4): 660-70. Mar 1 1998.
Comment
The above research results may be profoundly important regarding unravelling the mechanisms whereby cancer cells commit suicide and die. In the above case, the general of free radicals hydrogen peroxide is an important mechanism of apoptosis. So not all free radicals are bad, after all; some free radicals kill cancer cells.
