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Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells. | LitMetric

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

Cancer Lett

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA; Department of Surgery/Urology, University of Nebraska Medical Center, Omaha, NE, USA; School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. Electronic address:

Published: October 2014

AI Article Synopsis

Article Abstract

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150829PMC
http://dx.doi.org/10.1016/j.canlet.2014.07.002DOI Listing

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