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Antimicrobial Agents and Chemotherapy, February 2007, p. 488-494, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.01238-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cytotoxic Effect of Curcumin on Malaria Parasite Plasmodium falciparum: Inhibition of Histone Acetylation and Generation of Reactive Oxygen Species

Long Cui, Jun Miao, and Liwang Cui^*

Department of Entomology, The Pennsylvania State University, 501 ASI Building, University Park, Pennsylvania 16802

Received 3 October 2006/ Returned for modification 12 November 2006/ Accepted 26 November 2006

The emergence of multidrug-resistant parasites is a major concern for malaria control, and development of novel drugs is a high priority. Curcumin, a natural polyphenolic compound, possesses diverse pharmacological properties. Among its antiprotozoan activities, curcumin was potent against both chloroquine-sensitive and -resistant Plasmodium falciparum strains. Consistent with findings in mammalian cell lines, curcumin's prooxidant activity promoted the production in P. falciparum of reactive oxygen species (ROS), whose cytotoxic effect could be antagonized by coincubation with antioxidants and ROS scavengers. Curcumin treatment also resulted in damage of both mitochondrial and nuclear DNA, probably due to the elevation of intracellular ROS. Furthermore, we have demonstrated that curcumin inhibited the histone acetyltransferase (HAT) activity of the recombinant P. falciparum general control nonderepressed 5 (PfGCN5) in vitro and reduced nuclear HAT activity of the parasite in culture. Curcumin-induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggested that curcumin caused specific inhibition of the PfGCN5 HAT. Taken together, these results indicated that at least the generation of ROS and down-regulation of PfGCN5 HAT activity accounted for curcumin's cytotoxicity for malaria parasites.

Published ahead of print on 4 December 2006.

These authors contributed equally to the work.

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