PMID- 17122865
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20131121
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 21
IP  - 2
DP  - 2007 Feb
TI  - Reactive oxygen species mediate N-(4-hydroxyphenyl)retinamide-induced cell death 
      in malignant T cells and are inhibited by the HTLV-I oncoprotein Tax.
PG  - 261-9
AB  - N-(4-hydroxyphenyl)retinamide (HPR) is a synthetic retinoid that inhibits growth 
      of many human tumor cells, including those resistant to natural retinoids. HPR is 
      an effective chemopreventive agent for prostate, cervix, breast, bladder, skin 
      and lung cancers, and has shown promise for the treatment of neuroblastomas. We 
      have previously shown that HPR inhibits proliferation and induces apoptosis of 
      human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia 
      (ATL) and HTLV-I-negative malignant T cells, whereas no effect is observed on 
      normal lymphocytes. In this report, we identified HPR-induced reactive oxygen 
      species (ROS) generation as the key mediator of cell cycle arrest and apoptosis 
      of malignant T cells. HPR treatment of HTLV-I-negative malignant T cells was 
      associated with a rapid and progressive ROS accumulation. Pre-treatment with the 
      antioxidants vitamin C and dithiothreitol inhibited ROS generation, prevented 
      HPR-induced ceramide accumulation, cell cycle arrest, cytochrome c release, 
      caspase-activation and apoptosis. Therefore, anti-oxidants protected malignant T 
      cells from HPR-induced growth inhibition. The expression of the HTLV-I 
      oncoprotein Tax abrogated HPR-induced ROS accumulation in HTLV-I-infected cells, 
      which explains their lower sensitivity to HPR. Defining the mechanism of free 
      radical induction by HPR may support a potential therapeutic role for this 
      synthetic retinoid in ATL and HTLV-I-negative T-cell lymphomas.
FAU - Darwiche, N
AU  - Darwiche N
AD  - Department of Biology, American University of Beirut, Beirut, Lebanon. 
      darwichn@aub.edu.lb
FAU - Abou-Lteif, G
AU  - Abou-Lteif G
FAU - Bazarbachi, A
AU  - Bazarbachi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061123
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Gene Products, tax)
RN  - 0 (Reactive Oxygen Species)
RN  - 187EJ7QEXL (Fenretinide)
SB  - IM
MH  - Anticarcinogenic Agents/pharmacology
MH  - Cell Death/*drug effects
MH  - Fenretinide/*pharmacology
MH  - Gene Products, tax/*pharmacology
MH  - *Human T-lymphotropic virus 1
MH  - Humans
MH  - Leukemia, Myeloid, Acute
MH  - Reactive Oxygen Species/metabolism
MH  - T-Lymphocytes/drug effects/*physiology
MH  - U937 Cells
EDAT- 2006/11/24 09:00
MHDA- 2007/09/26 09:00
CRDT- 2006/11/24 09:00
PHST- 2006/11/24 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2006/11/24 09:00 [entrez]
AID - 2404472 [pii]
AID - 10.1038/sj.leu.2404472 [doi]
PST - ppublish
SO  - Leukemia. 2007 Feb;21(2):261-9. doi: 10.1038/sj.leu.2404472. Epub 2006 Nov 23.