Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells

Collection:
Clark Atlanta University Faculty Publications
Title:
Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells
Creator:
Lyons, Anastesia S.
Ingersoll, Matthew A.
Muniyan, Sakthivel
D'Cunha, Napoleon
Robinson, Tashika
Hoelting, Kyle
Dwyer, Jennifer G.
Biu, Xiu R.
Batra, Surinder K.
Lin, Ming-Fong
Date of Original:
2015-06-29
Subject:
African Americans--Education (Higher)--Georgia
Clark Atlanta University
Location:
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Medium:
articles
Type:
Text
Format:
application/pdf
Description:
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 castration-resistant 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.
Source: PLoS ONE
DOI: 10.1371/journal.pone.0131811
URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131811
Metadata URL:
http://hdl.handle.net/20.500.12322/cau.ir:2015_lyons_etal
Language:
eng
Original Collection:
Clark Atlanta University Faculty Publications
Holding Institution:
Clark Atlanta University
Rights:

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