Induction of apoptosis in human promyelocytic leukemia cells by a natural trachylobane diterpene.
BACKGROUND
Trachylobane diterpenes are secondary metabolites, quite rare in nature, and their bioactivities are poorly understood. Recently, we have described the cytotoxic activity of ent-trachyloban-3beta-ol isolated from the leaves of Croton zambesicus, a plant used in African folk medicine.


METHODS
Cell viability on several cell lines, cell morphology, DNA laddering, annexin Vand caspase-3 activation experiments were undertaken in order to analyse the cytotoxicty of trachylobane diterpene and to determine if this compound is able to induce apoptosis.


RESULTS
ent-Trachyloban-3beta-ol exerts a dose-dependent cytotoxic effect, which varies between cell lines. Induction of apoptosis in HL-60 cells could be detected at a concentration of 50 microM after 24-h treatment.


CONCLUSIONS
We show here, for the first time, that a trachylobane diterpene is able to induce apoptosis in human promyelocytic leukemia cells via caspase-3 activation in a concentration-dependent manner.
Block
S
S
Laboratoire de Pharmacognosie, Université Catholique de Louvain, UCL 72.30-CHAM, 1200 Bruxelles, Belgium.
Gerkens
P
P
Peulen
O
O
Jolois
O
O
Mingeot-Leclercq
M P
MP
De Pauw-Gillet
M Cl
MC
Quetin-Leclercq
J
J
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D029802:Croton / Q000737:chemistry; D004224:Diterpenes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010718:Phosphatidylserines / Q000378:metabolism
D004224:Diterpenes; D010718:Phosphatidylserines; C464952:trachyloban-3-ol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases