Serdemetan Antagonizes the Mdm2-HIF1α Axis Leading to Decreased Levels of Glycolytic Enzymes

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Sep 17

PMID 24040331

Citations 9

Authors

Jason A Lehman

Paula M Hauck

Jaimie M Gendron

Christopher N Batuello

Jacob A Eitel

Allan Albig

Madhavi P Kadakia

Lindsey D Mayo

Affiliations

Soon will be listed here.

Abstract

Serdemetan (JNJ-26854165), an antagonist to Mdm2, was anticipated to promote the activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also regulates numerous proteins involved in diverse cellular functions. We investigated if Serdemetan would alter the Mdm2-HIF1α axis and affect cell survival in human glioblastoma cells independently of p53. Treatment of cells with Serdemetan under hypoxia resulted in a decrease in HIF1α levels. HIF1α downstream targets, VEGF and the glycolytic enzymes (enolase, phosphoglycerate kinase1/2, and glucose transporter 1), were all decreased in response to Serdemetan. The involvement of Mdm2 in regulating gene expression of glycolytic enzymes raises the possibility of side effects associated with therapeutically targeting Mdm2.

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