Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)
Abstract
:Introduction
Results and Discussion
Induction of apoptosis in trypanosomes and leukemia cells (Jurkat APO-S)
Alkaloid (highest concentration tested) | Membrane depolarization | PCD/Apoptosis (DNA fragmentation) | |||
---|---|---|---|---|---|
Jurkat APO-S | T. b. brucei | Jurkat APO-S | Jurkat + z-VAD-fmk | T. b. brucei | |
Quinoline alkaloids | |||||
Cinchonidine (10-3 M) | na | 50% | 45% | 25% | EC50: 0.42 mM |
Cinchonine (10-4 M) | na | na | na | nd | 30% |
Quinidine (10-4 M) | na | na | na | nd | 45% |
Quinine (10-3 M) | 15% | 50% | 45% | 45% | EC50: 59.9 µM |
Isoquinoline alkaloids | |||||
α-Allocryptopine (10-4 M) | na | na | na | nd | 17% |
Aporphine (10-4 M) | nd | na | nd | nd | na |
Berberine (10-4 M) | 15% | 35% | na | na | EC50: 99.5 µM |
Boldine (10-4 M) | nd | na | nd | nd | na |
Chelerythrine (10-4 M) | 100% | 95% | 35% | 5% | EC50: 1.3 µM |
Chelidonine (10-4 M) | na | na | 30% | 12% | na |
Coralyne (10-4 M) | nd | na | nd | nd | na |
Emetine (2.5 x 10-4 M) | 5% | na | 10-5 M 45% | 10-5 M 16% | EC50: 9.8 µM |
Laudanosine (10-4 M) | nd | nd | nd | nd | EC50: 0.5 mM |
Noscapine (10-3 M) | nd | nd | nd | nd | EC50: 0.54 mM |
Papaverine (10-4 M) | na | 30% | 18% | 6% | 10% |
Protopine (10-4 M) | na | na | 10% | 4% | 30% |
Sanguinarine (10-5 M) | 65% | 50% | 5% | 5% | EC50: 4.8 µM |
Indole alkaloids | |||||
Ajmalicine (10-4 M) | nd | nd | nd | nd | 50% |
Ajmaline (10-4 M) | nd | nd | nd | nd | na |
Brucine (10-4 M) | nd | nd | nd | nd | na |
Ellipticine (10-4 M) | 100% | 90% | 15% | 10% | 10% |
Ergotamine (10-4 M) | nd | nd | nd | nd | EC50: 64 µM |
Gramine (10-4 M) | nd | nd | nd | nd | na |
Harmaline (10-4 M) | nd | nd | nd | nd | 45% |
Harman (10-4 M) | nd | nd | nd | nd | na |
Harmine (10-4 M) | 5% | 30% | 30% | 10% | EC50: 74 µM |
Physostigmine (10-3 M) | nd | nd | nd | nd | EC50: 0.54 mM |
Strychnine (10-5 M) | nd | nd | nd | nd | na |
Vinblastine (10-5 M) | na | nd | 35% | 15% | 40% |
Vincamine (10-4 M) | na | nd | na | na | na |
Vincristine (10-5 M) | na | nd | 40% | 20% | 35% |
Yohimbine (10-4 M) | nd | nd | nd | nd | na |
Steroidal alkaloids | |||||
α-Chaconine (10-5 M) | nd | nd | nd | nd | EC50: 2.4 µM |
Demissidine (10-4 M) | nd | nd | nd | nd | EC50: 14 µM |
α-Solanine (10-5 M) | na | na | na | nd | EC50: 8.5 mM |
Veratridine (10-4 M) | nd | nd | nd | nd | EC50: 43 µM |
Piperidine alkaloids | |||||
Arecoline (10-3 M) | nd | nd | nd | nd | 45% |
Coniine (10-4 M) | nd | nd | nd | nd | na |
Lobeline (10-4 M) | nd | nd | nd | nd | na |
Piperine (10-3 M) | 50% | 40% | 30% | 5% | EC50: 0.57 mM |
Pseudopellerine (10-3 M) | nd | nd | nd | nd | na |
Purine alkaloids | |||||
Caffeine (10-4 M) | nd | nd | nd | nd | na |
Theobromine (10-4 M) | nd | nd | nd | nd | na |
Theophylline (10-4 M) | nd | nd | nd | nd | na |
Tropane alkaloids | |||||
Hyoscyamine (10-3 M) | nd | nd | nd | nd | 32% |
Methylscopolamine (10-3 M) | nd | nd | nd | nd | na |
Tropine (10-3 M) | nd | nd | nd | nd | na |
Quinolizidine alkaloids | |||||
Cytisine (10-4 M) | nd | nd | nd | nd | na |
Lupanine (10-3 M) | nd | nd | nd | nd | na |
Sparteine (10-3 M) | nd | nd | nd | nd | na |
Other alkaloids | |||||
Aconitine (10-5 M) | nd | nd | nd | nd | na |
Capsaicine (10-5 M) | nd | nd | nd | nd | na |
Colchicine (10-4 M) | na | 40% | 50% | 22% | 50% |
Ephedrine (10-3 M) | nd | nd | nd | nd | na |
Nicotine (10-3 M) | nd | nd | nd | nd | na |
Controls | |||||
Actinomycin D (10-3 M) | nd | nd | 35% | 12% | nd |
CCCP (10-5 M) | 60% | 50% | nd | nd | EC50: 30 µM |
Staurosporine (5 x 10-5 M) | nd | nd | nd | nd | EC50: 29 nM |
Valinomycin (10-5 M) | 40% | 100% | 55% | 40% | 40% |
Alkaloid | Induction of apoptosis/PCD | Cytotoxicity | |||
---|---|---|---|---|---|
T. brucei | Jurkat APO-S 100 µM | HL60 MAC | T. brucei | HL60 | |
Chelerythrine | EC50: 1.3 µM | +++ | 1 µM | nd | nd |
Chaconine | EC50: 2.4 µM | nd | na | nd | nd |
Sanguinarine | EC50: 4.8 µM | + | 5 µM | EC50: 1.9 µM | EC50: 1.4 µM |
Emetine | EC50: 9.8 µM | +++ | 0.5 µM | EC50: 0.04 µM | EC50: 0.09 µM |
Demissidine | EC50: 14 µM | nd | nd | nd | nd |
Veratridine | EC50: 43 µM | nd | na | nd | nd |
Quinine | EC50: 59.9 µM | ++ | 500 µM | EC50: 4.9 µM | EC50: 126 µM |
Ergotamine | EC50: 64 µM | nd | 50 µM | EC50: 3.2 µM | EC50: 32 µM |
Harmine | EC50: 74 µM | ++ | 100 µM | nd | nd |
Berberine | EC50: 99.5 µM | na | 100 µM | EC50: 0.53 µM | EC50: 27 µM |
Cinchonidine | EC50: 420 µM | ++ | 100 µM | EC50: 7.1 µM | EC50: 169 µM |
Laudanosine | EC50: 500 µM | nd | na | nd | nd |
Noscapine | EC50: 540 µM | nd | 50 µM | nd | nd |
Piperine | EC50: 570 µM | ++ | 100 µM | EC50: >100 µM | nd |
Vinblastine | 10-5 M: 40% | +++ | 5 nM | nd | nd |
Vincristine | 10-5 M: 35% | +++ | 5 nM | nd | nd |
Colchicine | 10-4 M: 50% | +++ | 0.1 µM | EC50: 21 µM | nd |
Ajmalicine | 10-4 M: 50% | nd | 50 µM | nd | nd |
Harmaline | 10-4 M: 45% | nd | na | EC50: 30 µM | nd |
Quinidine | 10-4 M: 45% | na | na | EC50: 0.7 µM | EC50: 400 µM |
Cinchonine | 10-4 M: 30% | na | na | EC50: 1.2 µM | EC50: 382 µM |
Ellipticine | 10-4 M: 10% | ++ | 5 µM | nd | nd |
Alkaloid | Disturbance of Membrane fluidity | DNAintercalation | Protein biosynthesis inhibition | Microtubul inhibition | Neurotoxins |
---|---|---|---|---|---|
Berberine | na | ++ | ++ | na | + |
Chaconine | +++ | nd | + | na | + |
Cinchonidine | na | + | ++ | na | + |
Cinchonine | na | + | + | na | + |
Colchicine | + | nd | na | +++ | + |
Demissidine | +++ | nd | nd | nd | + |
Emetine | na | + | ++++ | na | + |
Ergotamine | na | ++ | + | nd | +++ |
Harmine | + | ++ | ++ | nd | +++ |
Quinidine | + | + | ++ | na | + |
Quinine | na | + | ++ | na | + |
Sanguinarine | + | +++ | nd | na | ++ |
Vinblastine | nd | ++ | nd | +++ | + |
Vincristine | nd | ++ | nd | +++ | + |
Experimental
Cell line and culture conditions
Culture of Trypanosoma b. brucei
Tested substances
Induction of apoptosis
Analysis of cell death
Flow cytometry analysis:
Determination of mitochondrial membrane potential
Data analysis
Acknowledgements
References
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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. https://doi.org/10.3390/molecules13102462
Rosenkranz V, Wink M. Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei). Molecules. 2008; 13(10):2462-2473. https://doi.org/10.3390/molecules13102462
Chicago/Turabian StyleRosenkranz, Vera, and Michael Wink. 2008. "Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)" Molecules 13, no. 10: 2462-2473. https://doi.org/10.3390/molecules13102462