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Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)
Heidelberg University, Institute of Pharmacy and Molecular Biotechnology. INF 364, 69120 Heidelberg, Germany
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Received: 30 June 2008; in revised form: 5 September 2008 / Accepted: 30 September 2008 / Published: 3 October 2008
(This article belongs to the Special Issue Alkaloids
Abstract: The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation.
Keywords: Trypanosomiasis; leukemia; Trypanosoma brucei; Jurkat APO-S; alkaloids; apoptosis; programmed cell death
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Rosenkranz, V.; Wink, M. Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei). Molecules 2008, 13, 2462-2473.
Rosenkranz V, Wink M. Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei). Molecules. 2008; 13(10):2462-2473.
Rosenkranz, Vera; Wink, Michael. 2008. "Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)." Molecules 13, no. 10: 2462-2473.