alpha-Bromoacrylamido N-substituted isatin derivatives as potent inducers of apoptosis in human myeloid leukemia cells.
A novel series of alpha-bromoacryloyl N-substituted isatin analogues were found to inhibit the growth and viability of human myeloid leukemia HL-60 and U-937 cells as well as human lymphoid leukemia MOLT-3 cells. Cell death induced by these molecules was preceded by a rapid release of cytochrome c from mitochondria into the cytosol and subsequent caspase activation involving caspase-3, to cleave poly(ADP-ribose) polymerase (PARP). These findings suggest that these compounds present antiproliferative activity which may be mediated by apoptosis caused by cytochrome c release and caspase activation in human leukemia cells.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara (Italy). rmr@unife.it
Baraldi
Pier Giovanni
PG
Cruz-Lopez
Olga
O
Preti
Delia
D
Bermejo
Jaime
J
Estévez
Francisco
F
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology*; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020298:U937 Cells
D000970:Antineoplastic Agents; D007510:Isatin; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3