NDLI: Statin derivatives as therapeutic agents for castration-resistant prostate cancer

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Statin derivatives as therapeutic agents for castration-resistant prostate cancer

Content Provider	Scilit
Author	Ingersoll, Matthew A. Miller, Dannah R. Martinez, October Wakefield, C. Brent Hsieh, Kuan-Chan Simha, M. Vijaya Kao, Chai-Lin Chen, Hui-Ting Batra, Surinder K. Lin, Ming-Fong
Copyright Year	2016
Description	Journal: Cancer letters Despite recent advances in modern medicine, castration-resistant prostate cancer remains an incurable disease. Subpopulations of prostate cancer cells develop castration-resistance by obtaining the complete steroidogenic ability to synthesize androgens from cholesterol. Statin derivatives, such as simvastatin, inhibit cholesterol biosynthesis and may reduce prostate cancer incidence as well as progression to advanced, metastatic phenotype. In this study, we demonstrate novel simvastatin-related molecules SVA, AM1, and AM2 suppress the tumorigenicity of prostate cancer cell lines including androgen receptor-positive LNCaP C-81 and VCaP as well as androgen receptor-negative PC-3 and DU145. This is achieved through inhibition of cell proliferation, colony formation, and migration as well as induction of S-phase cell-cycle arrest and apoptosis. While the compounds effectively block androgen receptor signaling, their mechanism of inhibition also includes suppression of the AKT pathway, in part, through disruption of the plasma membrane. SVA also possess an added effect on cell growth inhibition when combined with docetaxel. In summary, of the compounds studied, SVA is the most potent inhibitor of prostate cancer cell tumorigenicity, demonstrating its potential as a promising therapeutic agent for castration-resistant prostate cancer.
Related Links	https://manuscript.elsevier.com/S030438351630550X/pdf/S030438351630550X.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086260/pdf
ISSN	03043835
DOI	10.1016/j.canlet.2016.09.008
Journal	Cancer letters
Issue Number	1
Volume Number	383
Language	English
Publisher	Elsevier BV
Publisher Date	2016-12-01
Access Restriction	Open
Subject Keyword	Journal: Cancer letters Medicinal Chemistry Androgen Receptor
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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