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KMID : 0982820030020020116
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Journal of Lung Cancer
2003 Volume.2 No. 2 p.116 ~ p.122
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Association between Expression of NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Synergistic Effect of Ionizing Radiation and β-lapachone on Human Lung Cancer Cell Line (A549)
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Lee Sang-Wook
Park Heon Joo
Kim Jong-Hoon
Ahn Seung-Do
Shin Seong-Soo
Choi Eun-Kyung
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Abstract
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Purpose: β-lapachone (β-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. β-lap was an effective agent alone, and in conbination with radiation or taxol with low-level host toxicity. We investigated the cytotoxicity of β-lap against A459 human lung cancer cells as well as the combined effect of β-lap and ionizing radiation.
Materials and Methods: An incubation of A459, HN3 and HN9 cells with 5μM of β-lap for 4 h killed almost 90% of the clonogenic cells. Raidation and β-lap acted synergistically in including clonogenic cell death and apoptosis in A549 cells when β-lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5μM of β-lap starting 5 h after irradiation was as effective as that stating immediately after irradiation. The mechanisms of β-lap induced cell killing is supposed that β-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 β-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 β-lap in killing cancer cells is not due to radiosensitization by β-lap but to enhancement of β-lap cytotoxocity by radiation through upregulation of NQO1.
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KEYWORD
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A459, NQO1, Radiation
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