Abstract B31: Cell-based screening of novel anticancer molecules for prostate cancer

Abstract

Abstract Metastatic and mutant androgen receptor prostate cancer are still of major concern for chemotherapy, lacking an efficacious approach to tackle this life threatening disease. This is so, because of the resilience to androgen ablation therapy. To accomplish with that, new molecules for prostate cancer have been tested in different in vitro models by academic groups and pharmaceutical entrepreneurs. In this work, novel molecules were tested in cell line that do not express androgen receptor (DU145) or cells harboring the mutant androgen receptor (LNCaP). Mouse fibroblast (Balb-c 3T3) cells were also tested in this cell-based screening to check for selectivity. These novel molecules came from previous studies using computational medicinal chemistry tools regarding mutant androgen receptor, surviving and mTOR inhibitors. All biological results were compared with the reference molecules bicalutamide, rapamycin, doxorubicin and YM155. The first screening comprised MTT colorimetric assay, further confirmed by flow cytometry studies, including cell cycle analysis and apoptosis indicators. Several novel molecules presented activity according to the screenings using prostate cancer cell lines. YM155 (a survivin inhibitor) was the only active molecule from the reference set when using the DU145 cells. Besides that, YM155 was the most selective molecule from the whole compound series (composed by reference and test sets). These phenotypic screenings provided the first evidence of anticancer molecules amenable for further chemical optimization. Citation Format: Karen Cristina dos Santos, Isadora Malavolta, Andrei Leitao. Cell-based screening of novel anticancer molecules for prostate cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B31.