TY - JOUR
T1 - Overexpression of WW domain-containing oxidoreductase WOX1 preferentially induces apoptosis in human glioblastoma cells harboring mutant p53
AU - Chiang, Ming Fu
AU - Yeh, Shu Ting
AU - Liao, Hui Fen
AU - Chang, Nan Shan
AU - Chen, Yu Jen
N1 - Funding Information:
This study was supported by grant NSC 98-2314-B-195-004-MY3 from the National Science Council of Republic of China , Taipei, Taiwan.
PY - 2012/9
Y1 - 2012/9
N2 - Purpose: Human WWOX gene encoding WW domain-containing oxidoreductase, named WWOX, FOR, or WOX1, has been studied in various types of cancer cells and shown to be a tumor suppressor with pro-apoptotic properties. Mutation or gain-of-function of p53 in glioma cells is associated with resistance to radiation therapy and poor prognosis. In this study, we overexpressed WOX1 to examine the pro-apoptotic activity against human glioblastoma cells harboring mutant p53. Methods: Overexpression of WOX1 in glioblastoma cell lines and apoptosis-related assays were performed. Results: Our results showed that overexpressed WOX1 induced apoptosis of glioblastoma U373MG harboring mutant p53 by causing hypoploidy and DNA fragmentation. However, ectopic WOX1 had no effect with U87MG possessing wild type p53. Unlike temozolomide, WOX1 induced apoptosis of U373MG cells via a mitochondria-independent and caspase-3-independent pathway. Conclusions: Overexpression of WOX1 preferentially inhibited viability and induced apoptosis in human glioblastoma cells expressing mutant p53 via a mechanism independent of the intrinsic apoptotic pathway. Conceivably, the survival of human glioblastoma cells depends upon interactions between the gain-of-function of p53 and WOX1. This suggests that modulation of WOX1 expression may be a novel strategy for treating human glioblastoma cells with mutant p53.
AB - Purpose: Human WWOX gene encoding WW domain-containing oxidoreductase, named WWOX, FOR, or WOX1, has been studied in various types of cancer cells and shown to be a tumor suppressor with pro-apoptotic properties. Mutation or gain-of-function of p53 in glioma cells is associated with resistance to radiation therapy and poor prognosis. In this study, we overexpressed WOX1 to examine the pro-apoptotic activity against human glioblastoma cells harboring mutant p53. Methods: Overexpression of WOX1 in glioblastoma cell lines and apoptosis-related assays were performed. Results: Our results showed that overexpressed WOX1 induced apoptosis of glioblastoma U373MG harboring mutant p53 by causing hypoploidy and DNA fragmentation. However, ectopic WOX1 had no effect with U87MG possessing wild type p53. Unlike temozolomide, WOX1 induced apoptosis of U373MG cells via a mitochondria-independent and caspase-3-independent pathway. Conclusions: Overexpression of WOX1 preferentially inhibited viability and induced apoptosis in human glioblastoma cells expressing mutant p53 via a mechanism independent of the intrinsic apoptotic pathway. Conceivably, the survival of human glioblastoma cells depends upon interactions between the gain-of-function of p53 and WOX1. This suggests that modulation of WOX1 expression may be a novel strategy for treating human glioblastoma cells with mutant p53.
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U2 - 10.1016/j.biopha.2012.03.003
DO - 10.1016/j.biopha.2012.03.003
M3 - Article
C2 - 22898080
AN - SCOPUS:84866156432
SN - 0753-3322
VL - 66
SP - 433
EP - 438
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
IS - 6
ER -