Novel imidazopyridine derivatives possess anti-tumor effect on human castration-resistant prostate cancer cells

Matthew A. Ingersoll, Anastesia S. Lyons, Sakthivel Muniyan, Napoleon D'Cunha, Tashika Robinson, Kyle Hoelting, Jennifer G. Dwyer, Xiu R. Bu, Surinder Kumar Batra, Ming-Fong Lin

Research output: Contribution to journalArticle

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Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castrationresistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.

Original languageEnglish (US)
Article numbere0131811
JournalPloS one
Volume10
Issue number6
DOIs
StatePublished - Jun 29 2015

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Castration
Cell growth
prostatic neoplasms
castration
Phosphatidylinositol 3-Kinases
Androgens
Tumors
Prostatic Neoplasms
Cells
Derivatives
neoplasms
Cell adhesion
Cell proliferation
Androgen Receptors
Neoplasms
Phosphotransferases
therapeutics
phosphatidylinositol 3-kinase
androgens
cell growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Novel imidazopyridine derivatives possess anti-tumor effect on human castration-resistant prostate cancer cells. / Ingersoll, Matthew A.; Lyons, Anastesia S.; Muniyan, Sakthivel; D'Cunha, Napoleon; Robinson, Tashika; Hoelting, Kyle; Dwyer, Jennifer G.; Bu, Xiu R.; Batra, Surinder Kumar; Lin, Ming-Fong.

In: PloS one, Vol. 10, No. 6, e0131811, 29.06.2015.

Research output: Contribution to journalArticle

Ingersoll, MA, Lyons, AS, Muniyan, S, D'Cunha, N, Robinson, T, Hoelting, K, Dwyer, JG, Bu, XR, Batra, SK & Lin, M-F 2015, 'Novel imidazopyridine derivatives possess anti-tumor effect on human castration-resistant prostate cancer cells', PloS one, vol. 10, no. 6, e0131811. https://doi.org/10.1371/journal.pone.0131811
Ingersoll MA, Lyons AS, Muniyan S, D'Cunha N, Robinson T, Hoelting K et al. Novel imidazopyridine derivatives possess anti-tumor effect on human castration-resistant prostate cancer cells. PloS one. 2015 Jun 29;10(6). e0131811. https://doi.org/10.1371/journal.pone.0131811
Ingersoll, Matthew A. ; Lyons, Anastesia S. ; Muniyan, Sakthivel ; D'Cunha, Napoleon ; Robinson, Tashika ; Hoelting, Kyle ; Dwyer, Jennifer G. ; Bu, Xiu R. ; Batra, Surinder Kumar ; Lin, Ming-Fong. / Novel imidazopyridine derivatives possess anti-tumor effect on human castration-resistant prostate cancer cells. In: PloS one. 2015 ; Vol. 10, No. 6.
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