PGE1 inhibited daunorubicin-induced apoptosis of human leukemia cell line, U937.

Aoyama-Hayashi Etsuko, Obata Yushi, Masuzawa Aki, Nozaki Toshiko, Yamada Hidehiro

doi:10.2492/jsir1981.18.369

Daunorubicin (DNR), one of the chemotherapeutic agents for the treatment of leukemia, is known to induce apoptotic cell death of leukemia cells. Apoptosis of leukemia cells in vivo accompanies phagocytic response by macrophages, which is now known to produce various mediators including PGE₂. In the present study, we studied the effect of PGE₁, a PGE₂ analog, on the DNR-induced apoptosis of human leukemia cell line, U937.<BR>PGE₁ itself had no effect on the cell cycle of U937, but it inhibited DNR-induced apoptosis in a dose dependent manner. This inhibitory effect was mimicked by a membrane-permeable cAMP analog, db-cAMP, and forskolin. Furthermore, pretreatment of U937 cells with H-89, a protein kinase A inhibitor, reversed the inhibiting effect of PGE₁. When co-cultured with LPS-activated peripheral blood monocytes, DNR-treated U937 cells showed less apoptosis, which was augmented by inhibiting endogenous production of PGE₂ from LPS-activated monocytes when they are cultured with indomethacin. Therefore, it suggested that PGE₁ inhibited DNR-induced apoptosis through activated cAMP, PKA signaling pathway. These results clearly show that PGE₁ inhibition of DNR-induced apoptosis of U937 is mediated by cAMP/PKA signaling pathway and that endogenous production of PGE₂ by macrophages, which eliminate apoptotic cells by phagocytosis in vivo, attenuates DNR-induced apoptosis of U937 cells. The present study suggests that administration of cyclooxygenase inhibitor, such as indomethacin, enhances chemotherapeutic effect of DNR-induced apoptosis of leukemia cells.

PGE1 inhibited daunorubicin-induced apoptosis of human leukemia cell line, U937.

Bibliographic Information

Search this article

Description

Journal

References(21)*help

Keywords

Details 詳細情報について

Export

Report a problem