Document Detail

Inhibition of bladder tumor growth by 1,1-bis(3'-indolyl)-1-(p-substitutedphenyl)methanes: a new class of peroxisome proliferator-activated receptor gamma agonists.
MedLine Citation:
PMID:  16397256     Owner:  NLM     Status:  MEDLINE    
1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes containing p-trifluoromethyl (DIM-C-pPhCF3), p-t-butyl (DIM-C-pPhtBu), and phenyl (DIM-C-pPhC6H5) substituents have been identified as a new class of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists that exhibit antitumorigenic activity. The PPARgamma-active C-DIMs have not previously been studied against bladder cancer. We investigated the effects of the PPARgamma-active C-DIMs on bladder cancer cells in vitro and bladder tumors in vivo. In this study, the PPARgamma-active compounds inhibited the proliferation of KU7 and 253J-BV bladder cancer cells, and the corresponding IC50 values were 5 to 10 and 1 to 5 micromol/L, respectively. In the less responsive KU7 cells, the PPARgamma agonists induced caveolin-1 and p21 expression but no changes in cyclin D1 or p27; in 253J-BV cells, the PPARgamma agonists did not affect caveolin-1, cyclin D1, or p27 expression but induced p21 protein. In KU7 cells, induction of caveolin-1 by each of the PPARgamma agonists was significantly down-regulated after cotreatment with the PPARgamma antagonist GW9662. DIM-C-pPhCF3 (60 mg/kg thrice a week for 4 weeks) inhibited the growth of implanted KU7 orthotopic and s.c. tumors by 32% and 60%, respectively, and produced a corresponding decrease in proliferation index. Treatment of KU7 cells with DIM-C-pPhCF3 also elevated caveolin-1 expression by 25% to 30%, suggesting a role for this protein in mediating the antitumorigenic activity of DIM-C-pPhCF3 in bladder cancer.
Wassim Kassouf; Sudhakar Chintharlapalli; Maen Abdelrahim; Gina Nelkin; Stephen Safe; Ashish M Kamat
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-06     Completed Date:  2006-02-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  412-8     Citation Subset:  IM    
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Caveolin 1 / metabolism
Cell Cycle Proteins / metabolism
Cell Growth Processes / drug effects
Indoles / administration & dosage,  pharmacology*
Mice, Inbred BALB C
Mice, Nude
PPAR gamma / agonists*
Thiazolidinediones / administration & dosage,  pharmacology
Urinary Bladder Neoplasms / drug therapy*,  metabolism,  pathology
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/1,1-bis(3'-indolyl)-1-(4-t-butylphenyl)methane; 0/1,1-bis(3'-indolyl)-1-(4-trifluoromethylphenyl)methane; 0/Caveolin 1; 0/Cell Cycle Proteins; 0/Indoles; 0/PPAR gamma; 0/Thiazolidinediones; 122320-73-4/rosiglitazone

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