KMID : 0620920100420050327
|
|
Experimental & Molecular Medicine 2010 Volume.42 No. 5 p.327 ~ p.334
|
|
¥â-Lapachone suppresses radiation-induced activation of nuclear factor-¥êB
|
|
Dong Guang-Zhi
Oh Eun-Taex Lee Hye-Mi Park Moon-Taek Song Chang-Won
|
|
Abstract
|
|
|
Anticancer effects of ¥â-lapachone (¥â-lap) are due to generation of ROS and metabolic catastrophes as a result of NAD(P)H:quinone oxidoreductase (NQO1)-mediated futile cycling between the oxidized and reduced forms of ¥â-lap. It has been shown that NQO1 is also essential for the TNF-induced activation of NF-¥êB and that ¥â-lap suppresses the TNF-induced NF-¥êB activation. We investigated whether or not NQO1 is involved and ¥â-lap suppresses the radiation-induced NF-¥êB activation using A549 human lung cancer cells and NQO1-knock down A549 cells (shNQO1 A549 cells). Irradiation with 4 Gy markedly increased the DNA binding activity of NF-¥êB in A549 cells, but not in the shNQO1 A549 cells, thus demonstrating that NQO1 plays a pivotal role in irradiation-induced NF-¥êB activation. Treatment with 10 ¥ìM ¥â-lap for 4 h almost completely abrogated the radiation-induced increase in NF-¥êB activation and the transcription of NF-¥êB target genes such as bcl2, gadd45¥â and cyclinD1. Moreover, ¥â-lap markedly suppressed the activation of I¥êB kinase ¥ã (IKK¥ã) and the subsequent phosphorylation of I¥êB¥á, thereby inhibiting NF-¥êB activation. It is concluded that ¥â-lap suppresses the radiation-induced activation of NF-¥êB by interrupting the involvement of NQO1 in the activation of NF-¥êB, thereby inhibiting the transcription of survival signals. The radiosensitization caused by ¥â-lap may, in part, be attributed to ¥â-lap-induced suppression of NF-¥êB activation.
|
|
KEYWORD
|
|
ionizing radiation, NAD(P)H:quinone oxidoreductase, NF-¥êB, ¥â-lapachone
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|