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.

Related Articles

Vanita Noronha, Laboni Sarkar, Vijay Patil, Nandini Menon, Minit Shah, Akash Pawar, Oindrila Roy Chowdhury, Omshree Shetty, Anuradha Chougule, Pratik Chandrani, Rajiv Kaushal, Trupti Pai, Amit Janu, Nivedita Chakrabarty, Kumar Prabhash
Bivas Biswas, Nikhil S Ghadyalpatil, Shekar Patil, Amol Patel, Sandip Ganguly, Anvesh Rathore, Bhupesh Guleria, Cpalli Firdouse Tarannum, Joydeep Ghosh, Mary Sravani Kondapally, Ravi Thippeswamy, Shashidhara Haragadde Poppa Reddy, Somnath Roy
Goutam Santosh Panda, Vanita Noronha, Vijay Patil, Amit Joshi, Nandini Menon, Rajiv Kumar, Trupti Pai, Omshree Shetty, Amit Janu, Nivedita Chakrabarty, Nilendu Purandare, Sayak Dey, Kumar Prabhash
Eva Maria Ruiz de Castilla, Maurice Mayrides, Haydée González, Francisco Vidangossy, Tatiana Corbeaux, Nancy Ortiz, Claudia Amaya, Alexandra Nuñez, Diego Fernando Jimbo Jimbo, Adela Ayensa, Mayra Galindo, Karla Ruiz, Juan Manuel Pérez
Olaniyi A Olatunde, Modupeola O Samaila, Mohammed I Imam, Kasiemobi E Uchime, Suleiman E Dauda