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.
journal_name
Planta Medjournal_title
Planta medicaauthors
Lansiaux A,Bailly C,Houssier C,Colson P,De Pauw-Gillet MC,Frédérich M,Tits M,Angenot Ldoi
10.1055/s-2002-32889subject
Has Abstractpub_date
2002-07-01 00:00:00pages
591-5issue
7eissn
0032-0943issn
1439-0221journal_volume
68pub_type
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