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Title: Hydrazinobenzoylcurcumin inhibits androgen receptor activity and growth of castration-resistant prostate cancer in mice
Authors: Wu, Min
Kim, Sahn-Ho
Datta, Indrani
Levin, Albert
Dyson, Gregory
Li, Jing
Kaypee, Stephanie
Swamy, M. Mahadeva
Gupta, Nilesh
Kwon, Ho Jeong
Menon, Mani
Kundu, Tapas Kumar
Reddy, G. Prem-Veer
Keywords: Oncology
Cell Biology
Androgen receptor
castration-resistant prostate cancer
Serine 81 Phosphorylation
Issue Date: 2015
Publisher: Impact Journals LLC
Citation: Oncotarget
Wu, M.; Kim, S. H.; Datta, I.; Levin, A.; Dyson, G.; Li, J.; Kaypee, S.; Swamy, M. M.; Gupta, N.; Kwon, H. J.; Menon, M.; Kundu, T. K.; Reddy, G. P. V., Hydrazinobenzoylcurcumin inhibits androgen receptor activity and growth of castration-resistant prostate cancer in mice. Oncotarget 2015, 6 (8), 6136-6150.
Abstract: There is a critical need for therapeutic agents that can target the amino-terminal domain (NTD) of androgen receptor (AR) for the treatment of castration-resistant prostate cancer (CRPC). Calmodulin (CaM) binds to the AR NTD and regulates AR activity. We discovered that Hydrazinobenzoylcurcumin (HBC), which binds exclusively to CaM, inhibited AR activity. HBC abrogated AR interaction with CaM, suppressed phosphorylation of AR Serine81, and blocked the binding of AR to androgen-response elements. RNA-Seq analysis identified 57 androgen-regulated genes whose expression was significantly (p <= 0.002) altered in HBC treated cells as compared to controls. Oncomine analysis revealed that genes repressed by HBC are those that are usually overexpressed in prostate cancer (PCa) and genes stimulated by HBC are those that are often down-regulated in PCa, suggesting a reversing effect of HBC on androgenregulated gene expression associated with PCa. Ingenuity Pathway Analysis revealed a role of HBC affected genes in cellular functions associated with proliferation and survival. HBC was readily absorbed into the systemic circulation and inhibited the growth of xenografted CRPC tumors in nude mice. These observations demonstrate that HBC inhibits AR activity by targeting the AR NTD and suggest potential usefulness of HBC for effective treatment of CRPC.
Description: Restricted access
ISSN: 1949-2553
Appears in Collections:Research Papers (Tapas K. Kundu)

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