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Mol. Cells 2012; 33(4): 371-378

Published online April 30, 2012

https://doi.org/10.1007/s10059-012-2293-2

© The Korean Society for Molecular and Cellular Biology

Prostaglandin E2 Blocks Menadione-Induced Apoptosis through the Ras/Raf/Erk Signaling Pathway in Promonocytic Leukemia Cell Lines

Hyun-Seok Yeo1, Adeeb Shehzad, and Young Sup Lee*

School of life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea, 1LG Life Science, Iksan 570-350, Korea

Correspondence to : *Correspondence: yselee@knu.ac.kr

Received: December 27, 2011; Revised: January 30, 2012; Accepted: February 1, 2012

Abstract

Altered oxidative stress has long been observed in can-cer cells, and this biochemical property of cancer cells represents a specific vulnerability that can be exploited for therapeutic benefit. The major role of an elevated oxidative stress for the efficacy of molecular targeted drugs is under investigation. Menadione is considered an attractive model for the study of oxidative stress, which can induce apoptosis in human leukemia HL-60 cell lines. Prostaglandin E2 (PGE2) via its receptors not only promotes cell survival but also reverses apoptosis and promotes cancer progression. Here, we present evidence for the biological role of PGE2 as a protective agent of oxidative stress-induced apoptosis in monocytic cells. Pretreatment of HL-60 cells with PGE2 markedly ameliorated the menadione-induced apoptosis and inhibited the degradation of PARP and lamin B. The EP2 receptor antagonist AH6809 abrogated the inhibitory effect of PGE2, suggesting the role of the EP2/cAMP system. The PKA inhibitor H89 also reversed apoptosis and decreased the PKA activity that was elevated 10-fold by PGE2. The treatment of HL-60 cells with NAC or zinc chloride showed a similar protective effect as with PGE2 on menadione-treated cells. Furthermore, PGE2 activated the Ras/Raf/MEK pathway, which in turn initiated ERK activation, and ultimately protected menadione-induced apo-ptosis. These results imply that PGE2 via cell survival path-ways may protect oxidative stress-induced apoptosis in monocytic cells. This study warrants further pre-clinical investigation as well as application towards leukemia clinics.

Keywords apoptosis, menadione, oxidative stress, prostaglandin

Article

Research Article

Mol. Cells 2012; 33(4): 371-378

Published online April 30, 2012 https://doi.org/10.1007/s10059-012-2293-2

Copyright © The Korean Society for Molecular and Cellular Biology.

Prostaglandin E2 Blocks Menadione-Induced Apoptosis through the Ras/Raf/Erk Signaling Pathway in Promonocytic Leukemia Cell Lines

Hyun-Seok Yeo1, Adeeb Shehzad, and Young Sup Lee*

School of life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea, 1LG Life Science, Iksan 570-350, Korea

Correspondence to:*Correspondence: yselee@knu.ac.kr

Received: December 27, 2011; Revised: January 30, 2012; Accepted: February 1, 2012

Abstract

Altered oxidative stress has long been observed in can-cer cells, and this biochemical property of cancer cells represents a specific vulnerability that can be exploited for therapeutic benefit. The major role of an elevated oxidative stress for the efficacy of molecular targeted drugs is under investigation. Menadione is considered an attractive model for the study of oxidative stress, which can induce apoptosis in human leukemia HL-60 cell lines. Prostaglandin E2 (PGE2) via its receptors not only promotes cell survival but also reverses apoptosis and promotes cancer progression. Here, we present evidence for the biological role of PGE2 as a protective agent of oxidative stress-induced apoptosis in monocytic cells. Pretreatment of HL-60 cells with PGE2 markedly ameliorated the menadione-induced apoptosis and inhibited the degradation of PARP and lamin B. The EP2 receptor antagonist AH6809 abrogated the inhibitory effect of PGE2, suggesting the role of the EP2/cAMP system. The PKA inhibitor H89 also reversed apoptosis and decreased the PKA activity that was elevated 10-fold by PGE2. The treatment of HL-60 cells with NAC or zinc chloride showed a similar protective effect as with PGE2 on menadione-treated cells. Furthermore, PGE2 activated the Ras/Raf/MEK pathway, which in turn initiated ERK activation, and ultimately protected menadione-induced apo-ptosis. These results imply that PGE2 via cell survival path-ways may protect oxidative stress-induced apoptosis in monocytic cells. This study warrants further pre-clinical investigation as well as application towards leukemia clinics.

Keywords: apoptosis, menadione, oxidative stress, prostaglandin

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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