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.
Key words
Sungucine - isosungucine - plant alkaloids - DNA binding - DNA synthesis - apoptosis
-
Strychnos icaja
- Loganiaceae
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bailly@lille.inserm.fr
