PMID- 15729717
OWN - NLM
STAT- MEDLINE
DCOM- 20050721
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 115
IP  - 6
DP  - 2005 Jul 20
TI  - Retinoid-related molecule AGN193198 potently induces G2M arrest and apoptosis in 
      bladder cancer cells.
PG  - 917-23
AB  - The novel synthetic retinoid-related molecule 
      4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-propenyl]benzoic 
      acid (AGN193198) neither binds effectively to retinoic acid receptors (RARs) and 
      retinoid X receptors (RXRs) nor transactivates in RAR- and RXR-mediated reporter 
      assays. Even so, AGN193198 is potent in inducing apoptosis in human prostate and 
      breast carcinoma cells (Keedwell et al., Cancer Res 2004;64:3302-12). Here, we 
      extend these findings to show that AGN193198 potently and rapidly induces 
      apoptosis in bladder carcinoma cell lines. One micromolar of AGN193198 completely 
      abolished the growth of the transitional cell carcinoma lines UM-UC-3 and J82, 
      and the squamous cell carcinoma line SCaBER; the transitional cell papilloma line 
      RT-4 was slightly less sensitive to the growth inhibitory effect of AGN193198. 
      Treated cells accumulated in the G2M phase of the cell cycle. This was 
      accompanied by apoptosis, as revealed by staining cells for exposure of 
      phosphatidylserine at their surface (binding of Annexin V) and FACS analysis of 
      propidium iodide labeled cells. As reported for prostate cancer cells, AGN193198 
      provoked rapid activation of caspases-3 (by 6 hr), -8 (by 16 hr) and -9 (by 6 hr) 
      in bladder cancer cells. These findings suggest that AGN193198 and related 
      compounds, whose mechanism of action does not appear to involve RARs and RXRs, 
      may be useful in the treatment of bladder cancer.
CI  - Copyright 2005 Wiley-Liss, Inc.
FAU - Reitmair, Armin
AU  - Reitmair A
AD  - Department of Biological Sciences, Allergan, Inc., Irvine, CA, USA.
FAU - Shurland, Dixie-Lee
AU  - Shurland DL
FAU - Tsang, Kwok-Yin
AU  - Tsang KY
FAU - Chandraratna, Roshantha A S
AU  - Chandraratna RA
FAU - Brown, Geoffrey
AU  - Brown G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (AGN193198)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Carcinoma, Transitional Cell/*pathology
MH  - Cell Division/drug effects
MH  - Humans
MH  - Papilloma/*pathology
MH  - Quinolines/*pharmacology
MH  - Receptors, Retinoic Acid/metabolism
MH  - Retinoid X Receptors/metabolism
MH  - Tumor Cells, Cultured
MH  - Urinary Bladder Neoplasms/*pathology
EDAT- 2005/02/25 09:00
MHDA- 2005/07/22 09:00
CRDT- 2005/02/25 09:00
PHST- 2005/02/25 09:00 [pubmed]
PHST- 2005/07/22 09:00 [medline]
PHST- 2005/02/25 09:00 [entrez]
AID - 10.1002/ijc.20961 [doi]
PST - ppublish
SO  - Int J Cancer. 2005 Jul 20;115(6):917-23. doi: 10.1002/ijc.20961.