Planta Med 2002; 68(7): 591-595
DOI: 10.1055/s-2002-32889
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Apoptosis of HL-60 Leukemia Cells Induced by the Bisindole Alkaloids Sungucine and Isosungucine from Strychnos icaja

Amélie Lansiaux1 , Christian Bailly1 , Claude Houssier2 , Pierre Colson2 , Marie-Claire De Pauw-Gillet3 , Michel Frédérich4 , Monique Tits4 , Luc Angenot4
  • 1INSERM U-524 et Centre Oscar Lambret, Lille, France
  • 2Laboratoire de Chimie Macromoléculaire et Chimie Physique, Université de Liège, Belgium
  • 3Centre de Recherche en Cancérologie Expérimentale, Université de Liège, Belgium
  • 4Laboratoire de Pharmacognosie, Institut de Pharmacie, Université de Liège, Belgium
Weitere Informationen

Publikationsverlauf

Received: October 25, 2001

Accepted: December 24, 2001

Publikationsdatum:
22. Juli 2002 (online)

Abstract

Sungucine and isosungucine are two bisindole alkaloids isolated from the roots of the African plant Strychnos icaja Baillon. They both exhibit antiplasmodial activities but also show cytotoxic effects against human cancer cell lines. In order to elucidate their mechanism of action, we have investigated the interaction of the alkaloids with DNA and their capacity to inhibit nucleic acids and protein synthesis in the human HL-60 promyelocytic leukemia cell line. Cell treatment with both sungucine and isosungucine leads to the appearance of a hypo-diploid DNA content peak. Western blotting analysis reveals that the two alkaloids induce cleavage of the poly(ADP-ribose) polymerase (PARP) and promote the cleavage of a caspase-3 DEVD peptide substrate. The activation of the caspase cascade is accompanied with a fragmentation of DNA in cells, as revealed by the TUNEL assay. Altogether, the results shed light on the mechanism of action of these two plant alkaloids and identify signaling factors involved in (iso)sungucine-induced apoptosis in HL-60 cells.

References

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Dr. C. Bailly

INSERM U-524

Institut de Recherches sur le Cancer de Lille 1

Place de Verdun

59045 Lille

France

eMail: bailly@lille.inserm.fr

Fax: +33 320 16 92 29