Skip navigation
Skip navigation

Targeting of two aspects of metabolism in breast cancer treatment

Gang, Bevan; Dilda, Pierre J; Hogg, Phillip; Blackburn, Anneke

Description

Deregulated metabolism is gaining recognition as a hallmark of cancer cells, and is being explored for therapeutic potential. The Warburg effect is a metabolic phenotype that occurs in 90% of tumors, where glycolysis is favored despite the presence of oxygen. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor that can reverse the Warburg effect. PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) is a novel anti-mitochondrial agent that targets the adenine...[Show more]

dc.contributor.authorGang, Bevan
dc.contributor.authorDilda, Pierre J
dc.contributor.authorHogg, Phillip
dc.contributor.authorBlackburn, Anneke
dc.date.accessioned2015-12-13T22:34:49Z
dc.identifier.issn1538-4047
dc.identifier.urihttp://hdl.handle.net/1885/76301
dc.description.abstractDeregulated metabolism is gaining recognition as a hallmark of cancer cells, and is being explored for therapeutic potential. The Warburg effect is a metabolic phenotype that occurs in 90% of tumors, where glycolysis is favored despite the presence of oxygen. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor that can reverse the Warburg effect. PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) is a novel anti-mitochondrial agent that targets the adenine nucleotide transporter in mitochondria and is currently in clinical trials for solid tumors. We have investigated the targeting of two aspects of metabolism, using DCA to promote mitochondrial activity combined with PENAO to inhibit mitochondrial activity, in breast and other carcinoma cell lines. PENAO was effective at low uM concentrations in luminal (T-47D) and triple negative (MDA-MB-231) breast cancer cells, in normoxia and hypoxia. The cytotoxicity of PENAO was enhanced by DCA by a mechanism involving increased reactive oxygen species in both T-47D and MDA-MB-231 cells, however further investigations found it did not always involve PDK2 inhibition or reduction of the mitochondrial membrane potential, which are the accepted mechanisms for DCA induction of apoptosis. Nevertheless, DCA sensitized all cancer cell lines tested toward apoptosis of PENAO. DCA and PENAO are both currently in clinical trials and targeting cancer metabolism with these drugs may offer options for difficult to treat cancers.
dc.publisherLandes Bioscience
dc.sourceCancer Biology and Therapy
dc.titleTargeting of two aspects of metabolism in breast cancer treatment
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume15
dc.date.issued2014
local.identifier.absfor111200 - ONCOLOGY AND CARCINOGENESIS
local.identifier.ariespublicationU3488905xPUB5138
local.type.statusPublished Version
local.contributor.affiliationGang, Bevan, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDilda, Pierre J, University of New South Wales
local.contributor.affiliationHogg, Phillip, University of New South Wales
local.contributor.affiliationBlackburn, Anneke, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue11
local.bibliographicCitation.startpage1533
local.bibliographicCitation.lastpage1541
local.identifier.doi10.4161/15384047.2014.955992
dc.date.updated2015-12-11T09:24:18Z
local.identifier.scopusID2-s2.0-84918504063
local.identifier.thomsonID000348381900010
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Gang_Targeting_of_two_aspects_of_2014.pdf652.96 kBAdobe PDF    Request a copy
02_Gang_Targeting_of_two_aspects_of_2014.pdf648.29 kBAdobe PDF    Request a copy


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator