書誌事項
- タイトル別名
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- PGE1 inhibited daunorubicin-induced apoptosis of human leukemia cell line, U937.
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説明
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.
収録刊行物
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- 炎症
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炎症 18 (5), 369-376, 1998
日本炎症・再生医学会
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詳細情報 詳細情報について
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- CRID
- 1390282679762820736
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- NII論文ID
- 10009359560
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- NII書誌ID
- AN00357213
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- ISSN
- 18844006
- 03894290
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可
