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dc.contributor.authorCh'ng, J.
dc.contributor.authorLee, Y.
dc.contributor.authorGun, S.
dc.contributor.authorChia, W.
dc.contributor.authorChang, Z.
dc.contributor.authorWong, L.
dc.contributor.authorBatty, Kevin
dc.contributor.authorRussell, B.
dc.contributor.authorNosten, F.
dc.contributor.authorRenia, L.
dc.contributor.authorTan, K.
dc.date.accessioned2017-01-30T14:56:15Z
dc.date.available2017-01-30T14:56:15Z
dc.date.created2015-01-12T20:00:32Z
dc.date.issued2014
dc.identifier.citationCh'ng, J. and Lee, Y. and Gun, S. and Chia, W. and Chang, Z. and Wong, L. and Batty, K. et al. 2014. Validation of a chloroquine-induced cell death mechanism for clinical use against malaria. Cell Death and Disease. 5: e1305 (9 p.).
dc.identifier.urihttp://hdl.handle.net/20.500.11937/41899
dc.identifier.doi10.1038/cddis.2014.265
dc.description.abstract

An alternative antimalarial pathway of an ‘outdated’ drug, chloroquine (CQ), may facilitate its return to the shrinking list of effective antimalarials. Conventionally, CQ is believed to interfere with hemozoin formation at nanomolar concentrations, but resistant parasites are able to efflux this drug from the digestive vacuole (DV). However, we show that the DV membrane of both resistant and sensitive laboratory and field parasites is compromised after exposure to micromolar concentrations of CQ, leading to an extrusion of DV proteases. Furthermore, only a short period of exposure is required to compromise the viability of late-stage parasites. To study the feasibility of this strategy, mice malaria models were used to demonstrate that high doses of CQ also triggered DV permeabilization in vivo and reduced reinvasion efficiency. We suggest that a time-release oral formulation of CQ may sustain elevated blood CQ levels sufficiently to clear even CQ-resistant parasites.

dc.publisherNature Publishing Group
dc.titleValidation of a chloroquine-induced cell death mechanism for clinical use against malaria
dc.typeJournal Article
dcterms.source.volume5
dcterms.source.startPage1
dcterms.source.endPage9
dcterms.source.issn2041-4889
dcterms.source.titleCell Death and Disease
curtin.note

This article is published under the Open Access publishing model and distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by-nc-sa/3.0/ Please refer to the licence to obtain terms for any further reuse or distribution of this work.

curtin.departmentSchool of Pharmacy
curtin.accessStatusOpen access


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