Abstract 120: A study of in vitro and in vivo effects of a novel peptide and rhenium compounds on prostate cancer

Abstract

Abstract Emerging evidence suggests that acquisition of the epithelial-to-mesenchymal transition (EMT), a process that resembles the genesis of cancer stem-like cells, contributes to tumor aggressiveness and is mediated by deregulated expression of microRNAs (miRNAs), such as miR-200 and let-7 family. Loss of miR-200 expression results in the over-expression of Lin28B, which is prevalent in human Prostate Cancer( PCa) . Lin28B is also known to block the processing of another miRNA (pre-let-7 and pri-let-7), resulting in decreased mature let-7, thereby leads to increased Suz12 and EZH2 expression, which are important components of the polycomb repressive complex 2 (PRC2). Thus, over- expression of Lin28B and loss of miR-200 and let-7 appear to be responsible for PCa aggressiveness. A group of novel rhenium compounds have shown promising anti-cancer properties in various cancer cell lines tested in our laboratories. Our current investigations show that re-expression of miR-200b, miR-200c, and let-7 could be achieved by treating cells with our newly developed rhenium compounds by down-regulating the expression of Lin28B and EZH2. Based on our preliminary results, we hypothesize that over-expression of Lin28B leads to the acquisition of invasive and metastatic characteristics in PCa cells (EMT-phenotype cells) via down-regulation of miR-200b and miR-200c, resulting in increased expression of Suz12, ZEB1, and ZEB2. We also hypothesize that over-expression of Lin28B represses the maturation of let-7 family, leading to increased expression of EZH2, and these processes can be attenuated by treatment of cells with novel rhenium compounds in vitro. Our experiments were done on prostate cancer cell lines derived from both Caucasian(CA) and African American (AA)patients and also biopsy samples obtained from both CA and AA patients at Henry Ford Hospital and Karmanos Cancer Center of Wayne State University, Detroit, MI. We confirmed using gene expression studies by micro array and Real-Time PCR and then data analysis by Ingenuity software systemthe validity of our hypothesis and continued our research by testing one of these rhenium compounds-RPR1 on prostate cancer model of nude mice at Greenbaum Cancer Center(GCC) of University of Maryland at Baltimore. In vitro studies by Real -Time PCR, Flow Cytometry, Western Blotting ,Smart-Flare technology, cell death and proliferation assays along with inhibition of spheroid forming assays showed efficacy of these rhenium compounds as anti cancer agents. In vivo studies also showed decrease of tumor volume and mass ,no toxicity, thus efficacy of these novel drugs. ACKNOWLEDGEMENT: Supported by NIH- 3R01CA164318-03S1 and NIH-T-34-GM100831, a NSF-VESTEM award and NSF-LSAMP award . Citation Format: Hirendra N. Banerjee, Sasha Hodge, William Kahan, Santosh Mandal, David Weber, Rena Lapidus, Fazlul Sarkar, Somiranjan Ghosh. A study of in vitro and in vivo effects of a novel peptide and rhenium compounds on prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 120. doi:10.1158/1538-7445.AM2017-120