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KMID : 0624620150480020109
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BMB Reports
2015 Volume.48 No. 2 p.109 ~ p.114
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Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway
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Shehzad Adeeb
Lee Jae-Tae
Lee Young-Sup
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Abstract
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The COX-2/PGE2 pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, PGE2, in cancer survival remain unknown. Herein, we investigated PGE2-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with PGE2 activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. PGE2 not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of PGE2, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the PGE2-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that PGE2 signaling acts in an autocrine manner, and specific inhibition of PGE2 will provide a novel approach for the treatment of leukemia.
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KEYWORD
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Apoptosis, Autocrine signaling, Cyclooxygenase-2, Leukemia, Prostaglandine E2
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