Apoptosis induction in human cancer cells by sungucine from Strychnos icaja root.
Sungucine (SG) and isosungucine (ISG) are bisindole alkaloids characterized by a 5'-23 link between the two parts of the compounds, which are till now specific to Strychnos icaja. In this work, SG and ISG were submitted to the NCI's in vitro 60 human tumor cell line screen, where SG showed interesting selectivity (6X) against the tested leukemia cell lines. In HL60-treated cells, apoptosis was demonstrated by observation of apoptotic bodies formation, and phosphatidylserine exposition at cell surface. In HeLa-treated cells, the analysis of cellular cycle by flow cytometry showed G1 accumulation and a small sub-G1 peak that could be related to DNA fragmentation characteristic of apoptosis. The eventual role of p53 was analyzed using wild-type HCT-116 colon cancer cells. Nevertheless, p53 and Bax expression were not modified in SG-treated cells. The cleavage of PARP by caspase-3 protease proved that apoptosis was also induced in this line. These results demonstrate that SG induces apoptosis, but also necrosis, in human cancer cell lines.
Frederich
Michel
M
CPSNS, Laboratory of Pharmacognosy and Structural Chemistry, Department of Pharmacy, University of Liège, Avenue de l'Hôpital 1, B36, 4000 Liège, Belgium.
Bentires-Ali
Mohamed
M
Tits
Monique
M
Angenot
Luc
L
Heinen
Ernst
E
De Pauw-Gillet
Marie-Claire
MC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D009336:Necrosis; D018517:Plant Roots / Q000737:chemistry; D013331:Strychnine; D031451:Strychnos / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D026121:Indole Alkaloids; C464946:sungucine; D013331:Strychnine