ecancermedicalscience

Special Issue

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

28 Aug 2014
Rosemary A Poku, Felix Amissah, Randolph Duverna, Byron J Aguilar, Gebre-Egziabher Kiros, Nazarius S Lamango

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

Article metrics: 845 views
300
545

Related Articles

Lekha Madhavan Nair, KM Jagathnath Krishna, Aswin Kumar, Susan Mathews, John Joseph, Francis Vadakkumparambil James
Annu Rajpurohit, Nilendu Purandare, Aliasgar Moiyadi, Prakash Shetty, Abhishek Mahajan, Rajiv Kumar, Subhash Yadav, Naveen Munmudi, Ameya Puranik, Anil Tibdewal, Rahul Krishnarthy, Ankita Ahuja, Nandini Menon, Vanita Noronha, Amit Joshi, Vijay M Patil, Kumar Prabhash
Renata D’Alpino Peixoto, Duilio R Rocha-Filho, Rui F Weschenfelder, Juliana FM Rego, Rachel Riechelmann, Anelisa K Coutinho, Gustavo S Fernandes, Alexandre A Jacome, Aline C Andrade, Andre M Murad, Celso AL Mello, Diego SCG Miguel, Diogo BD Gomes, Douglas J Racy, Eduardo D Moraes, Eduardo H Akaishi, Elisangela S Carvalho, Evandro S Mello, Fauze Maluf Filho, Felipe JF Coimbra, Fernanda C Capareli, Fernando F Arruda, Fernando MAC Vieira, Flavio R Takeda, Guilherme CC Cotti, Guilherme LS Pereira, Gustavo A Paulo, Héber SC Ribeiro, Laercio G Lourenco, Marcela Crosara, Marcelo G Toneto, Marcos B Oliveira, Maria de Lourdes Oliveira, Maria Dirlei Begnami, Nora M Forones, Osmar Yagi, Patricia Ashton-Prolla, Patricia B Aguillar, Paulo CG Amaral, Paulo M Hoff, Raphael LC Araujo, Raphael P Di Paula Filho, Rene C Gansl, Roberto A Gil, Tulio EF Pfiffer, Tulio Souza, Ulysses Ribeiro Jr, Victor Hugo f Jesus, Wilson L Costa Jr, Gabriel Prolla
Silvia Francesca Maria Pizzoli, Giulia Marton, Paola Pricolo, Serena Oliveri, Paul Summers, Giuseppe Petralia, Gabriella Pravettoni
Sami Mahjoub Taha, Hsin-Yi Weng, Mohammed El Imam Mohammed, Yassin M Osman, N’sanh N’dri, Sulma I Mohammed, Dafalla Omer Abuidris