[en] Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, a well known African shrub or little tree. The roots contain quaternary alkaloids, which are used to make a curare-like arrow poison. However, tertiary alkaloids isolated from the same plant possess cytotoxic activities against mammalian cells and protozoa. The effect of ISP has been investigated on the growth and viability of HCT-116 colon cancer cells during their exponentially growing phase. ISP induced apoptotic cell death as shown by the translocation of phosphatidylserine from the inner layer to the outer layer of the plasma membrane, chromatin condensation, DNA fragmentation, and caspase-3 and -9 activation. ISP provoked also cell cycle arrest in the G(2)-M phase. We also showed that the expression of p53 was not modified in ISP-treated cells, but that p21 was induced in a p53-independent manner. Finally, we demonstrated that ISP did not affect the catalytic activity of human topoisomerases I and II. In conclusion, ISP, which promotes cell death by a p53-independent apoptotic pathway, could be an interesting lead for cancer chemotherapy.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Bentires-Alj, M.
Tits, Monique ; Université de Liège - ULiège > Département de pharmacie > Phytochimie et phytothérapie
Angenot, Luc ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Greimers, Roland ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Gielen, Jacques
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Language :
English
Title :
Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, induces cell cycle arrest and apoptosis in human colon cancer cells
Publication date :
March 2003
Journal title :
Journal of Pharmacology and Experimental Therapeutics
ISSN :
0022-3565
eISSN :
1521-0103
Publisher :
Amer Soc Pharmacology Experimental Therapeutics, Bethesda, United States - Maryland
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