Polyisoprenylated methylated protein methyl esterase as a putative drug target for androgen-insensitive prostate cancer

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DOI: 10.3332/ECANCER.2014.459

关键词: LNCaPCancer researchCell migrationCarboxylesterase 1ApoptosisPharmacologyProtein methylationCancerBiologyProstate cancerViability assay

摘要: Prostate cancer (CaP) is the most frequently diagnosed in US men, with an estimated 236,590 new cases and 29,720 deaths 2013. There exists need to identify biomarkers/therapeutic targets for early/companion diagnosis development of novel therapies against recalcitrant disease. Mutation overexpression-induced abnormal activities polyisoprenylated proteins have been implicated CaP. Polyisoprenylated methylated protein methyl esterase (PMPMEase) catalyses only reversible terminal reaction polyisoprenylation pathway may promote effects G on cell viability. In this review, potential role PMPMEase serve as a drug target androgen-insensitive CaP was determined. Specific were found be 3.5- 4.5-fold higher androgen-sensitive 22Rv1 androgen-dependent LNCaP 1.5- 9.8-fold castration-resistant DU 145 PC-3 cells compared normal WPE1-NA22 prostate cells. The inhibitor, L-28, induced apoptosis EC50 values ranging from 1.8 4.6 μM. activity following treatment L-28 followed similar profile, IC50 2.3 130 disrupted F-actin filament organisation at 5 μM inhibited migration 4-fold 2 Analysis tissue microarray expression revealed intermediate, strong, very strong staining 94.5% 92 adenocarcinoma trace weak normal-adjacent controls. data are indication that effective targeting through more potent agents lead successful metastatic

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