Interactions Between Docetaxel (Taxotere) and Plasmodium falciparum-Infected Erythrocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-08, Vol.91 (18), p.8472-8476
• Main Authors: Schrével, Joseph, Sinou, Véronique, Grellier, Philippe, Frappier, François, Guénard, Daniel, Potier, Pierre
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Docetaxel; Dose response relationship; Drug interactions; Erythrocyte invasion; Erythrocytes; Erythrocytes - drug effects; Erythrocytes - parasitology; Immunity (Disease); In Vitro Techniques; Inhibitory concentration 50; Malaria, Falciparum - drug therapy; Merozoites; Microtubules - drug effects; Paclitaxel - analogs & derivatives; Paclitaxel - pharmacology; Parasites; Parasitism; Plasmodium falciparum; Plasmodium falciparum - drug effects; Schizogony; Schizonts; Taxoids
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.18.8472

Taxotere (docetaxel) inhibits Plasmodium falciparum erythrocytic development in vitro at nanomolar concentrations, both in chloroquine-sensitive (F32/Tanzania) and chloroquine-resistant (FcB1/Colombia, FcR3/Gambia) strains. The dose-response assays performed on asynchronous cultures during 42 hr showed clear biphasic curves with a plateau from 50 μ M to 10 nM and a single sigmoid curve with a concentration inhibiting 50% of growth (IC50) of 3-6 nM observed after a 72-hr incubation. Addition of Taxotere to different stages of FcB1 revealed two types of targets: one type on ring/trophozoite-infected erythrocytes (RBCs), at the micromolar level, and another type on schizont-infected RBCs, at the nanomolar level. Preincubation of normal RBCs with Taxotere at micromolar concentrations inhibited the merozoite invasion of erythrocytes and parasite growth. These Taxotere-RBC interactions were stable, at least for 1 day. Pulse experiments of 5 hr with Taxotere efficiently inhibit parasite development regardless of the period of the parasite's erythrocytic life cycle. However, different cellular effects were obtained depending upon periods of drug incubations. The inhibition of P. falciparum development by Taxotere should provide additional strategies to block parasite development.