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Cyclooxygenase and Lipoxygenase Inhibitors Potentiate Antiproliferative, Apoptotic and Differentiation effects of TNFa on human leukemic HL-60 cells

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ŠTIKA Jiří VONDRÁČEK Jan HOFMANOVÁ Jiřina ŠIMEK Vladimír KOZUBÍK Alois

Rok publikování 2000
Druh Článek ve sborníku
Konference 11th European Students' Conference at the Charité Berlin
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Fyziologie
Popis Our results indicated that indomethacin alone has only minor effects on the measured parameters, however it potentiated (in concentration dependent manner) antiproliferative and apoptotic effects of TNFa, as well as CD11b/14 expression. NSE activity and ROI production after TNFa treatment was not influenced by indomethacin. After combined treatment of cells with indomethacin and TNFa an increased percentage of cells in S-phase of the cell cycle was observed. On the other hand, MK-886 alone dose-dependently reduced proliferation and viability of HL-60 cells, induced apoptosis and increased amount of cells in G1 phase of the cell cycle. These effects were further potentiated by combination with TNFa. Moreover, when combined with TNFa MK-886 significantly increased NSE activity, ROI production and CD11b/14 expression, i. e. it potentiated differentiation of HL-60 cells. In conclusion, while inhibition of cyclooxygenase potentiates the antiproliferative and the apoptotic effects of TNFa, inhibition of lipoxygenase significantly increases also the differentiation induced by TNFa. These results may be important for searching new strategies of antileukemic therapy.

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