Potentiation of anti-cancer effect of beta-lapachone by increasing cellular NQO1 expression

초록

Beta-Lapachone (B-lap), an extract from Lapacho trees, is a cytotoxic quinone against cancer cells. It has been proposed that NAD(P)H:quinone oxidoreductase(NQO1) catalyzes two-electrons reduction of B-lap using either NADH or NAD(P)H as electron donor. The resultant hydroquinone is unstable and oxidized to the original form of B-lap in the presence of oxygen resulting in a futile cycling between the quinone and hydroquinone. The resultant depletion of NADH or NAD(P)H and ATP levels leads to massive release of Ca2+ from endoplasmic reticulum, depolarixing mictochondrial membrane and release of cytochrome C, which then triggers signal transduction for cell death. Therefore, the cytotoxicity of B-lap is closely related to constitutive NQO1 level in carious cancer cells. Importantly, it has been observed that the cellular level of NQO1 can be increased by exposing cells to ionizing radiation.