J Lung Cancer.
2003 Dec;2(2):116-122.
Association between Expression of NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Synergistic Effect of Ionizing Radiation and beta-lapachone on Human Lung Cancer Cell Line (A549)
- Affiliations
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- 1Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, South Korea. ekchoi@amc.seoul.kr
- 2Department of Microbiology, College of Medicine, Inha University, Inchon, South Korea.
Abstract
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PURPOSE: beta-lapachone ( beta-lap) has cytotoxic effect in a number of human cancer cell lines and through a unuique apoptotic pathway that is dependent upon NQO1, a two-electron reductase. beta-lap was an effective agent alone, and in conbination with radiation or taxol with low-level host toxicity. We investigated the cytotoxicity of beta-lap against A459 human lung cancer cells as well as the combined effect of beta-lap and ionizing radiation.
MATERIALS AND METHODS
An incubation of A459, HN3 and HN9 cells with 5 M of beta-lap for 4 h killed almost 90% of the clonogenic cells. Raidation and beta-lap acted synergistically in including clonogenic cell death and apoptosis in A549 cells when beta-lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 M of beta-lap starting 5 h after irradiation was as effective as that stating immediately after irradiation. The mechanisms of beta-lap induced cell killing is supposed that beta-lap is activated by NAD(P)H: quinone-oxidoreductase (NQO1) in the cells followed by an elevation of cytosolic Ca2+ level and activation of proteases leading to apoptosis.
RESULTS
We observed that beta-lap killed human lung and head neck cancer cells by an apoptotic response significantly enhanced by NAD(P)H: quinone oxidoreductase (NQO1) enzymatic activity after 4 Gy irradiation.
CONCLUSION
Taken together, we may conclude that the synergistic interaction of radiation and beta-lap in killing cancer cells is not due to radiosensitization by beta-lap but to enhancement of beta-lap cytotoxocity by radiation through upregulation of NQO1
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