Suppression of peroxiredoxin 4 in glioblastoma cells increases apoptosis and reduces tumor growth.
Glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy, is incurable despite the best combination of current cancer therapies. For the development of more effective therapies, discovery of novel candidate tumor drivers is urgently needed. Here, we report that peroxiredoxin 4 (PRDX4) is a putative tumor driver. PRDX4 levels were highly increased in a majority of human GBMs as well as in a mouse model of GBM. Reducing PRDX4 expression significantly decreased GBM cell growth and radiation resistance in vitro with increased levels of ROS, DNA damage, and apoptosis. In a syngenic orthotopic transplantation model, Prdx4 knockdown limited GBM infiltration and significantly prolonged mouse survival. These data suggest that PRDX4 can be a novel target for GBM therapies in the future.
Dardinger Center for Neuro-Oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Tae Hyong
TH
Kim
Jieun
J
Song
Sheila R
SR
Alcantara Llaguno
Eric
E
Murnan
Sandya
S
Liyanarachchi
Kamalakannan
K
Palanichamy
Ji-Yeun
JY
Yi
Mariano Sebastian
MS
Viapiano
Ichiro
I
Nakano
Sung Ok
SO
Yoon
Hong
H
Wu
Luis F
LF
Parada
Chang-Hyuk
CH
Kwon
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004249:DNA Damage; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D054464:Peroxiredoxins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
D017382:Reactive Oxygen Species; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; C515981:Prdx4 protein, mouse