NAD(H): quinone oxidoreductasel mediated antitumor efect by β-lapachone and ionizing radiation

초록

Backpround : β-lapachone(β-lap), a natural o-naphthoquinone, presents in the bark of the lapacho tree, it is cytotoxic against a variety of human cancer and potentiates the anti-tumor effect of Taxol and radiation. β-lap triggers apoptosis in a munber of human cancer cell lines through a unique apoptotic pathway that is dependent upon NQO1, a twoelectron reductase. In the present study, we investigated the cytotoxicity of β-lap against human cells as well as the combined effect of β-lap and ionizing radiation for in vitro. Methods: Western blot analysis was carried out for NQO1 expression. Cell cycle analysis was performed on β-lap treated cells using PI staining and flow cytometry. Results: NQO1 expression directly correlated with sensitivity to a 4-h pulse of β-lap in various cancer cell lines, and the NQO1 inhibitor, dicoumarol, significantly protected NQO1-expressing cells from all aspects of β-lap toxicity. NQO1 levels significantly correlated with β-lap sensitivity. there was no apparent change in the cell cycle after β-lap treatment. However, β-lap inhibited G2 check point by irradiation. Conclusion: The synergistic interaction of radiation and β-lap in killing cancer cells is not due to radiosesitization by β-lap but to enhancement of β-lap cytotoxocity by radiation through up-refulation of NQO1. the fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferntially kill tumor cells using β-lap in combination with radiotherapy.