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

Sakthivel Muniyan, Yu Wei Chou, Matthew A. Ingersoll, Alexus Devine, Marisha Morris, Valerie A. Odero-Marah, Shafiq A. Khan, William G. Chaney, Xiu R. Bu, Ming Fong Lin

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalCancer Letters
Volume353
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Androgen receptor
  • Imidazopyridine
  • P66Shc
  • PI3K/Akt
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Muniyan, S., Chou, Y. W., Ingersoll, M. A., Devine, A., Morris, M., Odero-Marah, V. A., Khan, S. A., Chaney, W. G., Bu, X. R., & Lin, M. F. (2014). Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells. Cancer Letters, 353(1), 59-67. https://doi.org/10.1016/j.canlet.2014.07.002