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Molecules and Cells

, Volume 33, Issue 4, pp 371–378 | Cite as

Prostaglandin E2 blocks menadione-induced apoptosis through the Ras/Raf/Erk signaling pathway in promonocytic leukemia cell lines

  • Hyun-Seok Yeo
  • Adeeb Shehzad
  • Young Sup LeeEmail author
Article

Abstract

Altered oxidative stress has long been observed in cancer 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 apoptosis. These results imply that PGE2 via cell survival pathways 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 

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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2012

Authors and Affiliations

  1. 1.LG Life ScienceIksanKorea
  2. 2.School of life Sciences, College of Natural SciencesKyungpook National UniversityDaeguKorea

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