Document Detail


Carotenoids induce apoptosis in the T-lymphoblast cell line Jurkat E6.1.
MedLine Citation:
PMID:  12180130     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epidemiologically, a high-carotenoid intake via a fruit- and vegetable-rich diet is associated with a decreased risk of various forms of cancer. The mechanisms by which carotenoids exert this protective effect are controversial. In this study, we examined the potency of a range of carotenoids commonly found in human plasma to induce apoptosis in Jurkat E6.1 malignant T-lymphoblast cells. At a concentration of 20 microM, the order of potency to induce apoptosis after 24 h was: beta-carotene > lycopene > lutein > beta-cryptoxanthin = zeaxanthin. Canthaxanthin failed to induce apoptosis under these conditions. beta-Carotene induced apoptosis in a time- and concentration-dependent manner with a lowest effective concentration of about 3 microM. Pre-conditioning of beta-carotene for 72 h destroyed its pro-apoptotic activity almost completely, whereas degradation for 6 h or less did not, indicating that either beta-carotene itself and/or an early degradation product of beta-carotene are the death-inducing compounds. Apoptosis induced by beta-carotene was characterized by chromatin condensation and nuclear fragmentation, DNA degradation, PARP cleavage and caspase-3 activation. The antioxidant BO-653 inhibited the degradation of beta-carotene in vitro and significantly increased its cytotoxicity, indicating that a pro-oxidant effect of beta-carotene is unlikely to cause its pro-apoptotic activity. The induction of apoptosis in transformed cells by carotenoids may explain their protective effect against cancer formation in humans. Possible pathways for induction of apoptosis by carotenoids are discussed.
Authors:
Karin Müller; Keri L H Carpenter; Iain R Challis; Jeremy N Skepper; Mark J Arends
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical research     Volume:  36     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-08-15     Completed Date:  2003-01-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  791-802     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Blotting, Western
Canthaxanthin / pharmacology
Carotenoids / pharmacology
Caspase 3
Caspases / metabolism
Chemiluminescent Measurements
Chromatin / metabolism
Dose-Response Relationship, Drug
Humans
Jurkat Cells / drug effects,  metabolism,  pathology*
Lutein / pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Vitamin E / pharmacology
Xanthophylls
beta Carotene / analogs & derivatives*,  pharmacology*
Chemical
Reg. No./Substance:
0/Chromatin; 0/Xanthophylls; 127-40-2/Lutein; 1406-18-4/Vitamin E; 144-68-3/zeaxanthin; 36-88-4/Carotenoids; 472-70-8/cryptoxanthin; 502-65-8/lycopene; 514-78-3/Canthaxanthin; 7235-40-7/beta Carotene; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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