Other formats:
BibTeX
LaTeX
RIS
@article{387232,
author = {Vondráček, Jan and Štika, Jiří and Souček, Karel and Minksová, Kateřina and Bláha, Luděk and Hofmanová, Jiřina and Kozubík, Alois},
article_location = {Amsterdam},
article_number = {1},
language = {eng},
issn = {0014-2999},
journal = {European Journal of Pharmacology},
title = {Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells},
volume = {424},
year = {2001}
}
TY - JOUR
ID - 387232
AU - Vondráček, Jan - Štika, Jiří - Souček, Karel - Minksová, Kateřina - Bláha, Luděk - Hofmanová, Jiřina - Kozubík, Alois
PY - 2001
TI - Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells
JF - European Journal of Pharmacology
VL - 424
IS - 1
SP - 1
EP - 1
PB - Elsevier Science B.V.
SN - 00142999
N2 - We investigated whether and how could various modulators of arachidonic acid metabolism affect apoptosis induced by tumour necrosis factor-alpha (TNF-alpha) in human myeloid leukaemia HL-60 cells. These included arachinonyltrifluoromethyl ketone (AACOCF3; cytosolic phospholipase A2 inhibitor), indomethacin (cyclooxygenase inhibitor), MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethyl propanoic acid; 5-lipoxygenase-activating protein inhibitor), nordihydroguaiaretic acid (general lipoxygenase inhibitor), and arachidonic acid itself. Incubation of HL-60 cells with nordihydroguaiaretic acid resulted in apoptosis and it was characterised by mitochondria membrane depolarisation, release of cytochrome c from mitochondria into cytosol and activation of caspase-3. Indomethacin and nordihydroguaiaretic acid synergistically potentiated TNF-alpha-induced apoptosis, while arachidonic acid, AACOCF3 and MK-886 did not modulate its effects. Furthermore, indomethacin potentiated apoptosis in cells treated with a differentiating agent, all-trans retinoic acid, which induces resistance to TNF-alpha. However, the observed effects were probably not associated either with the cyclooxygenase- or lipoxygenase-dependent activities of indomethacin and nordihydroguaiaretic acid, respectively. Since indomethacin may reportedly activate peroxisome proliferator-activated receptors (PPARs), the effects of specific ligands of PPARs on apoptosis were studied as well. It was found that selective PPARs ligands had no effects on TNF-alpha-induced apoptosis. The findings suggest that arachidonic acid metabolism does not play a key role in regulation of apoptosis induced by TNF-alpha in the present model. Nevertheless, our data raise the possibility that indomethacin could potentially be used to improve the treatment of human myeloid leukaemia.
ER -
VONDRÁČEK, Jan, Jiří ŠTIKA, Karel SOUČEK, Kateřina MINKSOVÁ, Luděk BLÁHA, Jiřina HOFMANOVÁ and Alois KOZUBÍK. Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells. \textit{European Journal of Pharmacology}. Amsterdam: Elsevier Science B.V., 2001, vol.~424, No~1, p.~1-11. ISSN~0014-2999.
|
