Cytotoxicity and DNA binding properties of the plant alkaloid burasaine.
Burasaine is a plant alkaloid isolated from the roots of several species of the Burasaia genus endemic to Madagascar. It exhibits in vitro antiplasmodial activities but the molecular basis of this biological activity is not known. The strong structural similarity with the alkaloid berberine prompted us to postulate that burasaine could interact with DNA. To test this hypothesis, we investigated the mode of binding of burasaine to DNA and tested its cytotoxic potential toward human HL-60 leukemia cells. Its inhibitory activity toward topoisomerases I and II was also studied. Absorption and melting temperature measurements attested that burasaine forms stable complexes with DNA. The results of electric linear dichroism (ELD) spectroscopy may be interpreted either by an intercalation or by an external stacking parallel to the base pairs. The affinity of burasaine for DNA is slightly lower than that of berberine and this translates at the cellular level by a reduced cytotoxicity. Burasaine does not promote DNA cleavage by human topoisomerases I or II and this likely accounts for its very weak cytotoxic potential and its very modest effects on the cell cycle progression observed at high concentrations. The study identifies DNA as a potential bioreceptor for burasaine and contributes to a better understanding of the mechanism of action of benzoquinolizine alkaloids.
Kluza
Jérôme
J
INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France.
Baldeyrou
Brigitte
B
Colson
Pierre
P
Rasoanaivo
Philippe
P
Mambu
Lengo
L
Frappier
François
F
Bailly
Christian
C
D000465:Algorithms; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D001599:Berberine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D026942:DNA Topoisomerases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D010957:Plasmids / Q000187:drug effects; D013054:Spectrophotometry, Atomic; D013696:Temperature
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; C489232:burasaine; D001599:Berberine; D026942:DNA Topoisomerases