β-Actin-binding complementarity-determining region 2 of variable heavy chain from monoclonal antibody C7 induces apoptosis in several human tumor cells and is protective against metastatic melanoma.

The Journal of Biological Chemistry
Denise C ArrudaLuiz R Travassos

Abstract

Complementarity-determining regions (CDRs) from monoclonal antibodies tested as synthetic peptides display anti-infective and antitumor activities, independent of the specificity of the native antibody. Previously, we have shown that the synthetic peptide C7H2, based on the heavy chain CDR 2 from monoclonal antibody C7, a mAb directed to a mannoprotein of Candida albicans, significantly reduced B16F10 melanoma growth and lung colony formation by triggering tumor apoptosis. The mechanism, however, by which C7H2 induced apoptosis in tumor cells remained unknown. Here, we demonstrate that C7H2 interacts with components of the tumor cells cytoskeleton, being rapidly internalized after binding to the tumor cell surface. Mass spectrometry analysis and in vitro validation revealed that β-actin is the receptor of C7H2 in the tumor cells. C7H2 induces β-actin polymerization and F-actin stabilization, linked with abundant generation of superoxide anions and apoptosis. Major phenotypes following peptide binding were chromatin condensation, DNA fragmentation, annexin V binding, lamin disruption, caspase 8 and 3 activation, and organelle alterations. Finally, we evaluated the cytotoxic efficacy of C7H2 in a panel of human tumor cell lines. ...Continue Reading

References

May 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·V Buonassisi, J C Venter
Sep 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·M J OwenM J Crumpton
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M LeviB Wahren
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J MoroianuB L Vallee
Mar 1, 1996·Analytical Chemistry·A ShevchenkoM Mann
Dec 11, 1996·The American Journal of Physiology·M G LeveeD B Hinshaw
Feb 6, 1999·The Journal of Biological Chemistry·S C Posey, B E Bierer
Nov 26, 1999·Journal of Cellular Biochemistry·J Y RaoG P Hemstreet
Sep 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sergey ChernyshPhilippe Bulet
Jul 2, 2003·Amino Acids·Y L Janin
Aug 19, 2003·International Review of Cytology·Yosef GruenbaumAvital Enosh
Oct 7, 2003·American Journal of Clinical Oncology·David MurrayM Joan Allalunis-Turner
Nov 25, 2003·Nature Cell Biology·Boon Tin ChuaPeng Li
Jan 20, 2004·Cancer Research·Hao WangGerald A Soff
Jul 29, 2004·Current Medicinal Chemistry·W MaglianiL Polonelli
Sep 2, 2004·Cellular Microbiology·Elio CenciAnna Vecchiarelli
Dec 24, 2004·Journal of Cell Science·Vera DesMaraisJohn Condeelis
May 26, 2005·The Journal of General Virology·Caroline J HeapNigel J Dimmock
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Valentina Perissi, Michael G Rosenfeld
Aug 3, 2005·Nature Reviews. Molecular Cell Biology·Campbell W Gourlay, Kathryn R Ayscough
Feb 21, 2006·Experimental Parasitology·Dianella SavoiaLuciano Polonelli
Mar 16, 2006·The Biochemical Journal·Ho Lam TangHong Lok Lung
Dec 15, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lindsey A MilesRobert J Parmer
Feb 26, 2008·Trends in Biotechnology·Sujit K Bhutia, Tapas K Maiti
Jul 3, 2008·Cancer Research·Anna Maria GiammarioliMarina Pierdominici
Jul 11, 2008·The Biochemical Journal·Vernonica E Franklin-Tong, Campbell W Gourlay
Jun 13, 2009·Current Medicinal Chemistry·W MaglianiL Polonelli
Dec 17, 2009·Current Opinion in Supportive and Palliative Care·Dorothy Keefe, Andrea Stringer
Dec 19, 2009·Cell Death and Differentiation·J E LeadshamC W Gourlay
Apr 8, 2011·Current Pharmaceutical Biotechnology·David Barras, Christian Widmann

❮ Previous
Next ❯

Citations

Jun 30, 2015·Future Microbiology·Walter MaglianiLuciano Polonelli
Oct 12, 2016·Scientific Reports·Luciano PolonelliStefania Conti
Mar 4, 2020·Journal of Fungi·Camila BonicheCarlos Pelleschi Taborda
Mar 11, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Tecla CiociolaLuciano Polonelli
Feb 14, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Binoy MaitiSankar Maiti
Mar 23, 2018·Critical Reviews in Biochemistry and Molecular Biology·Federica IavaroneTiziana Cabras

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.