Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1998-6-9
|
| pubmed:abstractText |
Beta-Lapachone a novel topoisomerase inhibitor, has been found to induce apoptosis in various human cancer cells. In this study we report that a dramatic elevation of hydrogen peroxide (H2O2) in human leukemia HL-60 cells following 1 microM beta-lapachone treatment and that this increase was effectively inhibited by treatment with antioxidant N-acetyl-L-cysteine (NAC), ascorbic acid, alpha-tocopherol. NAC strongly prevented beta-lapachone-induced apoptotic characteristics such as DNA fragmentation and apoptotic morphology. However, treatment of HL-60 cells with another topoisomerase inhibitor camptothecin (CPT) did not induce H2O2 production as compared to untreated cells. NAC also failed to block CPT-induced apoptosis. Correlated with these findings, we found that cancer cell lines K562, MCF-7, and SW620, contained high level of intracellular glutathione (GSH), were not elevated in H2O2 and were resistant to apoptosis after treatment with beta-lapachone. In contrast, cancer cell lines such as, HL-60, U937, and Molt-4 which have lower level of GSH, were readily increased of H2O2 and were sensitive to this drug. Furthermore, ectopic overexpression of Bcl-2 in HL-60 cells also attenuated beta-lapachone-induced H2O2 and conferred resistance to beta-lapachone-induced cell death. Beta-Lapachone at the concentration as low as 0.25 microM effectively induced HL-60 cells to undergo monocytic differentiation, as evidenced by CD14 antigenicity and alpha-naphthyl acetate esterase activity. Again, the beta-lapachone-induced monocytic differentiation was suppressed by NAC. These results suggest that intracellular H2O2 generation plays a crucial role in beta-lapachone-induced cell death and differentiation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E,
http://linkedlifedata.com/resource/pubmed/chemical/beta-lapachone
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0891-5849
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
660-70
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:9559879-Acetylcysteine,
pubmed-meshheading:9559879-Antioxidants,
pubmed-meshheading:9559879-Apoptosis,
pubmed-meshheading:9559879-Ascorbic Acid,
pubmed-meshheading:9559879-Cell Differentiation,
pubmed-meshheading:9559879-DNA Fragmentation,
pubmed-meshheading:9559879-Drug Resistance,
pubmed-meshheading:9559879-Enzyme Inhibitors,
pubmed-meshheading:9559879-Glutathione,
pubmed-meshheading:9559879-Humans,
pubmed-meshheading:9559879-Hydrogen Peroxide,
pubmed-meshheading:9559879-Leukemia, Promyelocytic, Acute,
pubmed-meshheading:9559879-Monocytes,
pubmed-meshheading:9559879-Naphthoquinones,
pubmed-meshheading:9559879-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:9559879-Topoisomerase I Inhibitors,
pubmed-meshheading:9559879-Tumor Cells, Cultured,
pubmed-meshheading:9559879-Vitamin E
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone-induced apoptosis and differentiation in human leukemia cells.
|
| pubmed:affiliation |
Institute of Anatomy, School of Life Sciences, National Yang-Ming University, Taiwan.
|
| pubmed:publicationType |
Journal Article
|