Document Detail


Identification of a small molecule class to enhance cell-cell adhesion and attenuate prostate tumor growth and metastasis.
MedLine Citation:
PMID:  19276166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of calcitonin (CT) and its receptor (CTR) is elevated in advanced prostate cancer, and activated CT-CTR autocrine axis plays a pivotal role in tumorigenicity and metastatic potential of multiple prostate cancer cell lines. Recent studies suggest that CT promotes prostate cancer metastasis by reducing cell-cell adhesion through the disassembly of tight and adherens junctions and activation of beta-catenin signaling. We attempted to identify a class of molecules that enhances cell-cell adhesion of prostate cells and reverses the disruptive actions of CT on tight and adherens junctions. Screening several compounds led to the emergence of phenyl-methylene hydantoin (PMH) as a lead candidate that can augment cell-cell adhesion and abolish disruptive actions of CT on junctional complexes. PMH reduced invasiveness of PC-3M cells and abolished proinvasive actions of CT. Importantly, PMH did not display significant cytotoxicity on PC-3M cells at the tested doses. I.p. administered PMH and its S-ethyl derivative remarkably decreased orthotopic tumor growth and inhibited the formation of tumor micrometastases in distant organs of nude mice. PMH treatment also reduced the growth of spontaneous tumors in LPB-Tag mice to a significant extent without any obvious cytotoxic effects. By virtue of its ability to stabilize cell junctions, PMH could reverse the effect of CT on junctional disruption and metastasis, which strengthens the possibility of using PMH as a potential drug candidate for CT-positive androgen-independent prostate cancers.
Authors:
Girish V Shah; Anbalagan Muralidharan; Shibu Thomas; Mitan Gokulgandhi; Mudit Mudit; Mohammad Khanfar; Khalid El Sayed
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-10
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  8     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-06-08     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  509-20     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, University of Louisiana College of Pharmacy, 1800 Bienville Drive, Monroe, LA 71209, USA. shah@ulm.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / classification,  isolation & purification*,  pharmacology*,  therapeutic use
Cell Adhesion / drug effects
Cell Proliferation / drug effects*
Humans
Hydantoins / pharmacology,  therapeutic use
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Mice, Transgenic
Neoplasm Metastasis
Prostatic Neoplasms / pathology*
Small Molecule Libraries / analysis,  classification
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
P20RR16456/RR/NCRR NIH HHS; R01CA96534/CA/NCI NIH HHS; R56 CA096534-05A1/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Hydantoins; 0/Small Molecule Libraries
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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