Inhibitors of arachidonic acid metabolism potentiate tumour
necrosis factor-alpha-induced apoptosis in HL-60 cells

J 2001

Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells

VONDRÁČEK, Jan; Jiří ŠTIKA; Karel SOUČEK; Kateřina MINKSOVÁ; Luděk BLÁHA et al.

Základní údaje

Originální název

Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells

Autoři

VONDRÁČEK, Jan; Jiří ŠTIKA ; Karel SOUČEK; Kateřina MINKSOVÁ; Luděk BLÁHA; Jiřina HOFMANOVÁ a Alois KOZUBÍK

Vydání

European Journal of Pharmacology, Amsterdam, Elsevier Science B.V. 2001, 0014-2999

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30102 Immunology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 2.164

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/01:00005239

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000170224200001

Změněno: 8. 1. 2002 16:37, Mgr. Jiří Štika, Ph.D.

Anotace

V originále

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.

Návaznosti

GA312/98/P011, projekt VaV

Název: Úloha metabolismu kyseliny arachidonové v apoptóze indukované TNF-alfa a anti-Fas v průběhu diferenciace buněk lidské leukemické linie HL-60

GA524/99/0694, projekt VaV

Název: Vysoce nenasycené mastné kyseliny a cytokiny - jejich úloha pro zachování homeostázy na úrovni buněčných populací

Citovat

VONDRÁČEK, Jan; Jiří ŠTIKA; Karel SOUČEK; Kateřina MINKSOVÁ; Luděk BLÁHA; Jiřina HOFMANOVÁ a Alois KOZUBÍK. Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells. European Journal of Pharmacology. Amsterdam: Elsevier Science B.V., 2001, roč. 424, č. 1, s. 1-11. ISSN 0014-2999.

@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 a 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, roč.~424, č.~1, s.~1-11. ISSN~0014-2999.

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