RGD peptide-induced apoptosis in human leukemia HL-60 cells requires caspase-3 activation.
RGD motif-containing peptides have been used in various studies of cell adhesion and growth. We report that RGD triggered apoptosis at a concentration of 1 mmol/L, whereas RAD-containing peptides failed to induce apoptosis in HL-60 cells. RGD-treated cells revealed internucleosomal DNA fragmentation. Western blot reveals caspase-3 activation in RGD peptide-treated cells. A caspase-3 inhibitor z-VAD-FMK completely blocked the apoptosis, but a caspase-1 inhibitor (Ac-YVAD-CMK) and caspase-2 inhibitor (z-VDVAD-FMK) did not block the apoptosis, suggesting that caspase-3 might have a critical role in the execution process of apoptosis induced by RGD. RGD peptides have been used extensively to inhibit tumor metastasis. Our results should help in further understanding the RGD peptide-induced apoptosis, which is important since RGD peptides have a potential role in therapies of the future.
Anuradha
C D
CD
Regional Environment Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Kanno
S
S
Hirano
S
S
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D017302:Annexins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D009842:Oligopeptides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C047981:arginyl-glycyl-aspartic acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases