title: Pim-1 knockdown potentiates paclitaxel-induced apoptosis in human hormone-refractory prostate cancers through inhibition of NHEJ DNA repair.
abstract: The knockdown of Pim-1 or inhibition of Pim-1 activity significantly increased γ-H2A.X expression. The effect was correlated to apoptosis and was attributed to the inhibition of nonhomologous DNA-end-joining (NHEJ) repair activity supported by the following observations: (1) inhibition of ATM and DNA-PKcs activities, (2) down-regulation of Ku expression and nuclear localization and (3) decrease of DNA end-binding of both Ku70 and Ku80. The data suggest that Pim-1 plays a crucial role in the regulation of NHEJ repair. In the absence of Pim-1, the ability of DNA repair significantly decreases when exposed to paclitaxel, leading to severe DNA damage and apoptosis.
authors.affiliation: School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Road, Taipei 100, Taiwan.
authors.forename: Jui-Ling
authors.initials: JL
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Road, Taipei 100, Taiwan.
authors.forename: Pui-Kei
authors.initials: PK
authors.lastname: Leong
authors.affiliation: School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Road, Taipei 100, Taiwan.
authors.forename: Yunn-Fang
authors.initials: YF
authors.lastname: Ho
authors.affiliation: School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Road, Taipei 100, Taiwan.
authors.forename: Lih-Ching
authors.initials: LC
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Road, Taipei 100, Taiwan.
authors.forename: Pin-Hsuan
authors.initials: PH
authors.lastname: Lu
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.affiliation: School of Pharmacy, National Taiwan University, No. 1, Sect. 1, Jen-Ai Road, Taipei 100, Taiwan. Electronic address: jhguh@ntu.edu.tw.
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059766:DNA End-Joining Repair / Q000187:drug effects*; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics*; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008870:Microtubules / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen; D017239:Paclitaxel