RGD peptides induce apoptosis by direct caspase-3 activation. Academic Article uri icon


  • Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD-containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF-7, which has a functional deletion of the caspase-3 gene, we confirm that caspase-3 is required for RGD-mediated cell death. In addition to an RGD motif, pro-caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate-methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis.

published proceedings

  • Nature

altmetric score

  • 213.5

author list (cited authors)

  • Buckley, C. D., Pilling, D., Henriquez, N. V., Parsonage, G., Threlfall, K., Scheel-Toellner, D., ... Salmon, M.

citation count

  • 364

complete list of authors

  • Buckley, CD||Pilling, D||Henriquez, NV||Parsonage, G||Threlfall, K||Scheel-Toellner, D||Simmons, DL||Akbar, AN||Lord, JM||Salmon, M

publication date

  • February 1999

published in