Document Detail

5E, 8Z, 11Z, 14Z-eicosatetraenoic acid, a novel trans isomer of arachidonic acid, causes G1 phase arrest and induces apoptosis of HL-60 cells.
MedLine Citation:
PMID:  16211211     Owner:  NLM     Status:  MEDLINE    
Trans arachidonic acid isomers (trans-AA) constitute a new group of trans fatty acids (trans-FA) generated in vivo via endogenous cis-trans isomerization stimulated by the NO2 radical. Because both NO2 and trans-FA have been implicated as causative factors in cancer, we studied the effect of the trans-AA isomers on proliferation and viability of human promyelocytic (HL-60) cells. The four trans arachidonic (trans-AA) acid isomers synthesized by us have been presently tested with respect to their competence to affect the proliferation and viability of human promyeolocytic HL-60 cells in culture. The data demonstrate that one of the isomers, 5,6-trans-AA, showed distinct activity by targeting cell progression through the cell cycle and inducing apoptosis. The effects were time- and concentration-dependent: the cytostatic effect of 5E-AA was observed at 10 microM following 72 h of treatment. This effect was manifested as a perturbation of cell progression through G1 phase, indicating the 'on' activation of the G1 checkpoint as evidenced by the flow- and laser scanning-cytometry techniques. Apoptotic cells were identified by comparison of their morphology, DNA fragmentation, caspase activation and collapse of mitochondrial potential with control cells. These observations suggested that 5E-AA induced a mitochondrial pathway of apoptosis. There was no evidence of cell-cycle phase specificity in induction of apoptosis by 5E-AA, as the cells showing highly fragmented DNA or caspase-3 activation were distributed in all phases of the cycle. The data suggest that 5E-AA may have at least two targets: one that is cell-cycle specific and associated with the observed arrest in the G1 phase and another, unrelated to the cell cycle, which is responsible for triggering apoptosis indiscriminately, regardless of cycle phase I.
Kavita Jain; Uzzal Roy; Barbara Ardelt; U M Krishna; J R Falck; Piotr Pozarowski; Jan Kunicki; Zbigniew Darzynkiewicz; Michael Balazy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of oncology     Volume:  27     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-07     Completed Date:  2005-12-15     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1177-85     Citation Subset:  IM    
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MeSH Terms
Apoptosis / drug effects*
Arachidonic Acid / pharmacology*
DNA Damage
G1 Phase / drug effects*
HL-60 Cells
Mitochondria / drug effects,  physiology
Grant Support
5R01 CA028704/CA/NCI NIH HHS; 5R01 GM062453/GM/NIGMS NIH HHS; 5R01 GM31728/GM/NIGMS NIH HHS; R01 CA028704/CA/NCI NIH HHS; R01 CA028704-27/CA/NCI NIH HHS
Reg. No./Substance:
27YG812J1I/Arachidonic Acid

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

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