Publication: Validation of a chloroquine-induced cell death mechanism for clinical use against malaria.
Accepted Date
2014-05-20
Issued Date
2014-06
Copyright Date
2014
Resource Type
Language
eng
ISSN
2041-4889 (electronic)
Rights
Mahidol University
Rights Holder(s)
Cell death & disease
Bibliographic Citation
Ch'ng JH, Lee YQ, Gun SY, Chia WN, Chang ZW, Wong LK. et al.Validation of a chloroquine-induced cell death mechanism for clinical use against malaria. Cell Death Dis. 2014 Jun 26;5:e1305.
Suggested Citation
Ch’ng, J-H, Lee, Y-Q, Gun, SY, Chia, W-N, Chang, Z-W, Wong, L-K, Batty, KT, Russell, B, Nosten, F, Renia, L, Tan, KS-W Validation of a chloroquine-induced cell death mechanism for clinical use against malaria.. Ch'ng JH, Lee YQ, Gun SY, Chia WN, Chang ZW, Wong LK. et al.Validation of a chloroquine-induced cell death mechanism for clinical use against malaria. Cell Death Dis. 2014 Jun 26;5:e1305.. doi:10.1038/cddis.2014.265. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/796
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Title
Validation of a chloroquine-induced cell death mechanism for clinical use against malaria.
Corresponding Author(s)
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An alternative antimalarial pathway of an 'outdated' drug, chloroquine (CQ), may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.