PT  - JOURNAL ARTICLE
AU  - Michel Frédérich
AU  - Mohamed Bentires-Alj
AU  - Monique Tits
AU  - Luc Angenot
AU  - Roland Greimers
AU  - Jacques Gielen
AU  - Vincent Bours
AU  - Marie-Paule Merville
TI  - Isostrychnopentamine, an Indolomonoterpenic Alkaloid from<em>Strychnos usambarensis</em>, Induces Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells
AID  - 10.1124/jpet.102.044867
DP  - 2003 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1103--1110
VI  - 304
IP  - 3
4099  - http://jpet.aspetjournals.org/content/304/3/1103.short
4100  - http://jpet.aspetjournals.org/content/304/3/1103.full
SO  - J Pharmacol Exp Ther2003 Mar 01; 304
AB  - 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 G2-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. The American Society for Pharmacology and Experimental Therapeutics