PMID- 15126374
OWN - NLM
STAT- MEDLINE
DCOM- 20040623
LR  - 20191108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 9
DP  - 2004 May 1
TI  - A retinoid-related molecule that does not bind to classical retinoid receptors 
      potently induces apoptosis in human prostate cancer cells through rapid caspase 
      activation.
PG  - 3302-12
AB  - Synthetic retinoid-related molecules, such as N-(4-hydroxyphenyl)retinamide 
      (fenretinide) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic 
      acid (CD437) induce apoptosis in a variety of malignant cells. The mechanism(s) 
      of action of these compounds does not appear to involve retinoic acid receptors 
      (RARs) and retinoid X receptors (RXRs), although some investigators disagree with 
      this view. To clarify whether some retinoid-related molecules can induce 
      apoptosis without involving RARs and/or RXRs, we used 
      4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-E-propenyl] 
      benzoic acid (AGN193198) that neither binds effectively to RARs and RXRs nor 
      transactivates in RAR- and RXR-mediated reporter assays. AGN193198 potently 
      induced apoptosis in prostate, breast, and gastrointestinal carcinoma cells and 
      in leukemia cells. AGN193198 also abolished growth (by 50% at 130-332 nM) and 
      induced apoptosis in primary cultures established from prostatic carcinoma (13 
      patients) and gastrointestinal carcinoma (1 patient). Apoptosis was induced 
      rapidly, as indicated by mitochondrial depolarization and DNA fragmentation. 
      Molecular events provoked by AGN193198 included activation of caspase-3, -8, -9, 
      and -10 (by 4-6 h) and the production of BID/p15 (by 6 h). These findings show 
      that caspase-mediated induction of apoptosis by AGN193198 is RAR/RXR-independent 
      and suggest that this compound may be useful in the treatment of prostate cancer.
FAU - Keedwell, Richard G
AU  - Keedwell RG
AD  - Division of Immunity and Infection, University of Birmingham Medical School, 
      Edgbaston, Birmingham, United Kingdom.
FAU - Zhao, Yi
AU  - Zhao Y
FAU - Hammond, Lisette A
AU  - Hammond LA
FAU - Qin, Suofu
AU  - Qin S
FAU - Tsang, Kwok-Yin
AU  - Tsang KY
FAU - Reitmair, Armin
AU  - Reitmair A
FAU - Molina, Yanira
AU  - Molina Y
FAU - Okawa, Yumiko
AU  - Okawa Y
FAU - Atangan, Larissa I
AU  - Atangan LI
FAU - Shurland, Dixie-Lee
AU  - Shurland DL
FAU - Wen, Kaisheng
AU  - Wen K
FAU - Wallace, D Michael A
AU  - Wallace DM
FAU - Bird, Roger
AU  - Bird R
FAU - Chandraratna, Roshantha A S
AU  - Chandraratna RA
FAU - Brown, Geoffrey
AU  - Brown G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (AGN193198)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Isoenzymes)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antineoplastic Agents/metabolism/pharmacology
MH  - Apoptosis/*drug effects/physiology
MH  - Caspases/*metabolism
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Isoenzymes/metabolism
MH  - Jurkat Cells
MH  - Male
MH  - Prostatic Neoplasms/*drug therapy/enzymology/metabolism/pathology
MH  - Quinolines/metabolism/*pharmacology
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinoid X Receptors
MH  - Retinoids/metabolism/*pharmacology
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation/drug effects
EDAT- 2004/05/06 05:00
MHDA- 2004/06/24 05:00
CRDT- 2004/05/06 05:00
PHST- 2004/05/06 05:00 [pubmed]
PHST- 2004/06/24 05:00 [medline]
PHST- 2004/05/06 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-2763 [doi]
PST - ppublish
SO  - Cancer Res. 2004 May 1;64(9):3302-12. doi: 10.1158/0008-5472.can-03-2763.