Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) is Pyruvylated During 3-bromopyruvate Mediated Cancer Cell Death

Overview

Journal Anticancer Res

Specialty Oncology

Date 2010 Jan 2

PMID 20044597

Citations 67

Authors

Shanmugasundaram Ganapathy-Kanniappan

Jean-Francois H Geschwind

Rani Kunjithapatham

Manon Buijs

Josephina A Vossen

Irina Tchernyshyov

Robert N Cole

Labiq H Syed

Pramod P Rao

Shinichi Ota

Mustafa Vali

Affiliations

Soon will be listed here.

Abstract

Background: The pyruvic acid analog 3-bromopyruvate (3BrPA) is an alkylating agent known to induce cancer cell death by blocking glycolysis. The anti-glycolytic effect of 3BrPA is considered to be the inactivation of glycolytic enzymes. Yet, there is a lack of experimental documentation on the direct interaction of 3BrPA with any of the suggested targets during its anticancer effect.

Methods And Results: In the current study, using radiolabeled ((14)C) 3BrPA in multiple cancer cell lines, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as the primary intracellular target of 3BrPA, based on two-dimensional (2D) gel electrophoretic autoradiography, mass spectrometry and immunoprecipitation. Furthermore, in vitro enzyme kinetic studies established that 3BrPA has marked affinity to GAPDH. Finally, Annexin V staining and active caspase-3 immunoblotting demonstrated that apoptosis was induced by 3BrPA.

Conclusion: GAPDH pyruvylation by 3BrPA affects its enzymatic function and is the primary intracellular target in 3BrPA mediated cancer cell death.

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