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Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells
- Source :
- Cancer Letters. 353:59-67
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
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.
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Time Factors
genetic structures
Pyridines
Antineoplastic Agents
Apoptosis
Article
Androgen deprivation therapy
Prostate cancer
Cell Movement
Prostate
Cell Line, Tumor
Internal medicine
LNCaP
medicine
Humans
Clonogenic assay
Protein Kinase Inhibitors
PI3K/AKT/mTOR pathway
Cell Proliferation
Phosphoinositide-3 Kinase Inhibitors
Dose-Response Relationship, Drug
business.industry
Cell growth
Imidazoles
Androgen Antagonists
medicine.disease
eye diseases
Prostatic Neoplasms, Castration-Resistant
Endocrinology
medicine.anatomical_structure
Oncology
Receptors, Androgen
Cancer cell
Cancer research
Phosphatidylinositol 3-Kinase
business
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 353
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....81bb23ddc1dfa0004e3f459a7eadee9b