PMID- 14712289
OWN - NLM
STAT- MEDLINE
DCOM- 20040324
LR  - 20131121
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 18
IP  - 3
DP  - 2004 Mar
TI  - N-(4-hydroxyphenyl)retinamide induces growth arrest and apoptosis in 
      HTLV-I-transformed cells.
PG  - 607-15
AB  - N-(4-hydroxyphenyl)retinamide (HPR) is a synthetic retinoid that inhibits growth 
      and induces apoptosis in many human cell lines. We explored the effects of HPR on 
      human T-cell lymphotropic virus type I (HTLV-I)-positive and HTLV-I-negative 
      malignant T-cell lines, most of which are resistant to all-trans retinoic acid. 
      Clinically achievable concentrations of HPR caused a dramatic inhibition of cell 
      proliferation, G(0)/G(1) arrest, and massive apoptosis in all tested malignant T 
      cells, while no effect was observed on resting or activated normal lymphocytes. 
      Interestingly, HTLV-I-negative cell lines were significantly more sensitive to 
      HPR compared to HTLV-I-positive and Tax-transfected cells. In HTLV-I-negative 
      cells only, HPR-induced apoptosis was associated with ceramide accumulation, 
      sharp decrease in mitochondrial membrane potential, and activation of caspases 8, 
      9 and 3, and could be partially reverted by the caspase inhibitor z-VAD 
      suggesting that Tax protects infected cells from ceramide accumulation and 
      caspase-mediated apoptosis. In HTLV-I-positive cells, HPR treatment rapidly 
      induced proteasomal-mediated degradation of p21, downregulated cyclin D(1), and 
      upregulated bax protein levels. These findings support a potential therapeutic 
      role for HPR in both HTLV-I-associated adult T-cell leukemia/lymphoma (ATL) and 
      HTLV-I-negative peripheral T-cell lymphomas.
FAU - Darwiche, N
AU  - Darwiche N
AD  - Department of Biology, American University of Beirut, Beirut, Lebanon. 
      darwichn@aub.edu.lb
FAU - Hatoum, A
AU  - Hatoum A
FAU - Dbaibo, G
AU  - Dbaibo G
FAU - Kadara, H
AU  - Kadara H
FAU - Nasr, R
AU  - Nasr R
FAU - Abou-Lteif, G
AU  - Abou-Lteif G
FAU - Bazzi, R
AU  - Bazzi R
FAU - Hermine, O
AU  - Hermine O
FAU - de The, H
AU  - de The H
FAU - Bazarbachi, Ali
AU  - Bazarbachi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BAX protein, human)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin D)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 187EJ7QEXL (Fenretinide)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspases/metabolism
MH  - Cell Division/drug effects
MH  - Cell Line, Transformed
MH  - *Cell Transformation, Viral
MH  - Cyclin D
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/metabolism
MH  - Fenretinide/*pharmacology
MH  - Human T-lymphotropic virus 1/*physiology
MH  - Humans
MH  - Proto-Oncogene Proteins/metabolism
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - T-Lymphocytes/metabolism/*pathology/virology
MH  - Tumor Cells, Cultured
MH  - bcl-2-Associated X Protein
EDAT- 2004/01/09 05:00
MHDA- 2004/03/25 05:00
CRDT- 2004/01/09 05:00
PHST- 2004/01/09 05:00 [pubmed]
PHST- 2004/03/25 05:00 [medline]
PHST- 2004/01/09 05:00 [entrez]
AID - 2403245 [pii]
AID - 10.1038/sj.leu.2403245 [doi]
PST - ppublish
SO  - Leukemia. 2004 Mar;18(3):607-15. doi: 10.1038/sj.leu.2403245.