title: Selenium-induced apoptosis-like cell death in Plasmodium falciparum.
abstract: Plasmodium falciparum has for some time been developing resistance against known anti-malarial drugs, and therefore a new drug is urgently needed. Selenium (Se), an essential trace element, in the form of inorganic Se, selenite (SeO32-), has been reported to have an anti-plasmodial effect, but its mechanism is still unclear. In the present study, we evaluated the anti-plasmodial effect of several Se compounds against P. falciparum in vitro. The anti-plasmodial effect of several Se compounds was analysed and their apoptosis-inducing activity was evaluated by morphological observation, DNA fragmentation assay and mitochondrial function analysis. SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial effects with 50% inhibition concentration at 9, 10, 45, and 65 μm, respectively, while selenate and methylselenocysteine up to 100 μm have no effect on parasite growth. The effective Se compounds caused the parasites to become shrunken and pyknotic and significantly increased mitochondrial damage against P. falciparum compared to the untreated control. In conclusion, SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial activities that induce apoptosis-like cell death in P. falciparum, and the anti-plasmodial effects of Se seem to be based on its chemical forms. The apoptosis-like cell-death mechanism in P. falciparum can be beneficial to respond to the growing problem of drug resistance.
authors.affiliation: Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Eka W
authors.initials: EW
authors.lastname: Suradji
authors.affiliation: Gunma University Graduate School of Health Sciences, 3-39-15 Showa-machi, Maebashi 371-8514, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hatabu
authors.affiliation: Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Yamazaki
authors.affiliation: Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Rizky
authors.initials: R
authors.lastname: Abdulah
authors.affiliation: Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Minato
authors.initials: M
authors.lastname: Nakazawa
authors.affiliation: Gunma University Graduate School of Health Sciences, 3-39-15 Showa-machi, Maebashi 371-8514, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nakajima-Shimada
authors.affiliation: Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koyama
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012643:Selenium / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D006454:Hemoglobins; D012643:Selenium