An Investigation To Study The Role Of Novel Rhenium Compounds On Onco Mir'S And Oncogenes Involved In Epithelial Mesenchymal Transition Of Prostate Cancer Cell Lines Derived From African American And Caucasian Patients

In this research, we seek to evaluate the efficacy of novel rhenium compounds as a novel targeted agent against prostate cancer (PCa) in pre-clinical model system. Since the incidence and aggressiveness of Pca is more prevalent in African Americans (AA) patients than Caucasian Americans (CA), we first assessed the relevance of genes Lin28B, EZH2, miR-200, and let-7 expression in human PCa tissue specimens for characterizing tumor aggressiveness, since these genes are involved in the process and also epithelial-mesenchymal transition(EMT).We also assessed whether these markers are deregulated by rhenium compounds using PCa cell lines. We tested the two novel rhenium compounds ie. Rhenium pentylcarbonato complexes (RPC), fac-(CO)3(a-diimine)ReOC(O)OC5H11 (where, a-diimines are 2,2’-bipyridyl and neocuproin for anticancer properties on PCa cell lines for apoptosis and cell death, and their bioactivity for anti-proliferative, anti-migratory and antispheroid forming capabilities, respectively on EO6-AA and MDA,Pca cell lines(from AA patients) and LNCAP,PC3 (from CA patients). We also studied the expression of miR-146a in these cell lines and Pca tissue specimens, since it is reported to be overexpressed in cancer cells for tumor survival advantage, regulated by down-regulating iNOS, the nitric oxide synthesizing gene. Our initial results of Real Time PCR,Western Blotting,MTT assay,smart flare assay,flow cytometry, in situ cytochemistry(TUNEL) and spheroid forming assays showed that these drugs have cytotoxic,anti proliferative and anti spheroid forming properties,can induce apoptosis in the Pca cell lines tested and can downregulate some of the onco miR9s and onco genes involved in Pca aggressiveness and EMT conversions as tested by the expression profiles of miRNAs (miR-200b, miR-200c, and let-7 family) by RT-PCR, and the protein expression of EZH2, Suz12, and Lin-28B by Western Blots. It is important to emphasize here that an estimated 40,000 men die of PCa every year in the US and each year about 60,000 men will develop castrate resistant PCa for which newer drugs are needed. Therefore, our work will contribute towards the development of a novel therapy that may translate into an effective treatment regimen against PCa and is highly relevant to the mission of both basic and translational cancer researchers. ACKNOWLEDGEMENT: Supported by a NCI disability supplement to NIH- grant# R01CA164318 and NIH-MARC NIGMS,grant# 5 T34 GM 100831-4.We are grateful to Dr.Li, Dr.S.Banerjee and Ms.S.Ali of Detroit Medical Center,MI,USA for their support and help in conducting this research. Citation Format: Hirendra N. Banerjee, Jameel Joyner, Alexis Barfield, B Morris, D Bell, William Kahan, Monet Stevenson, D Crummity, K Prabhakaran, Santosh Mandal, Fazlul Sarkar. An investigation to study the role of novel rhenium compounds on onco miR9s and oncogenes involved in epithelial mesenchymal transition of prostate cancer cell lines derived from African American and Caucasian patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4831.