Skip to main content
Log in

RGD peptide-induced apoptosis in human leukemia HL-60 cells requires caspase-3 activation

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allen RT, Hunter WJ, Agrawal DK. Morphological and biochemical characterisation and analysis of apoptosis. J Pharmacol Toxicol. 1997;37:215-28.

    Article  CAS  Google Scholar 

  • Buckley CD, Pilling D, Henriquez NV, et al. RGD-peptides induce apoptosis by direct caspase-3 activation. Nature. 1999;397:534-9.

    Article  PubMed  CAS  Google Scholar 

  • Carson DA, Ribeiro JM. Apoptosis and disease. Lancet. 1993; 341:1251-4.

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Wang J, Fu B, Yu L. RGD-containing peptides trigger apoptosis in glomerular mesangial cells of adult human kidneys. Biochem Biophys Res Commun. 1997;234:594-9.

    Article  PubMed  CAS  Google Scholar 

  • Earnshaw WC. Nuclear changes in apoptosis. Curr Opin Cell Biol. 1995;7:337-43.

    Article  PubMed  CAS  Google Scholar 

  • Fadok VA, Voelker DR, Campbell PA, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148:2207-16.

    PubMed  CAS  Google Scholar 

  • Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124:619-26.

    Article  PubMed  CAS  Google Scholar 

  • Gerschenson LE, Rotello RJ. Apoptosis: a different type of cell death. FASEB J. 1992;6:2450-5.

    PubMed  CAS  Google Scholar 

  • Jacobson MD. Programmed cell death: a missing link is found. Trends Cell Biol. 1997;7:467-9.

    Article  PubMed  CAS  Google Scholar 

  • Koopman G, Reutelingsperger CPM, Kuitjen GAM. Annexin V for flow cytometric detection of phosphatidyl serine expression of B cells undergoing apoptosis. Blood. 1995;84: 1415-19.

    Google Scholar 

  • Meredith JE, Schwartz MA. Integrins, adhesion and apoptosis. Trends Cell Biol. 1997;7:146-50.

    Article  CAS  PubMed  Google Scholar 

  • Nicholson DW, Thornberry NA. Caspases: killer proteases. Trends Biochem Sci. 1997;22:299-306.

    Article  PubMed  CAS  Google Scholar 

  • Pasqualini R, Koivunen E, Ruoslahti E. A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins. J Cell Biol. 1995;130:1189-96.

    Article  PubMed  CAS  Google Scholar 

  • Porter AG, Janicke RU. Death substrates come alive. Bioessays. 1997;19:501-7.

    Article  PubMed  CAS  Google Scholar 

  • Ruoslahti E. RGD and other recognition sequences for-integrins. Ann Rev Cell Dev Biol. 1996;12:697-715.

    Article  CAS  Google Scholar 

  • Ruoslahti E, Pierschbacher MD. Arg-Gly-Asp: a verasatile cell recognition signal. Cell. 1986;44:517-8.

    Article  PubMed  CAS  Google Scholar 

  • Salvesen GS, Dixit VM. Caspases: intracellular signalling by proteolysis. Cell. 1997;91:443-6.

    Article  PubMed  CAS  Google Scholar 

  • Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998;281:1312-16.

    Article  PubMed  CAS  Google Scholar 

  • Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol. 1995;184:39-51.

    Article  CAS  Google Scholar 

  • Werb Z. ECM and cell surface proteolysis: regulating cellular ecology. Cell. 1997;91:439-42.

    Article  PubMed  CAS  Google Scholar 

  • Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980;284:555-6.

    Article  PubMed  CAS  Google Scholar 

  • Wyllie AH, Kerr JFR, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251-306.

    Article  PubMed  CAS  Google Scholar 

  • Xia Z, Bergstrand A, Depierre JW, Nassberger L. The anti-depressants imipramine, clomipramine and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999; 13:338-47.

    Article  PubMed  CAS  Google Scholar 

  • Zou H, Henzel WJ, Liu XS, Lutschg A, Wang XD. APAF-1, a human protein homologous to C-elegans ced-4, participates in cytochrome-c dependent activation of caspase-3. Cell. 1997;90:405-13.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anuradha, C., Kanno, S. & Hirano, S. RGD peptide-induced apoptosis in human leukemia HL-60 cells requires caspase-3 activation. Cell Biol Toxicol 16, 275–283 (2000). https://doi.org/10.1023/A:1026758429238

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026758429238

Navigation