Noncationic peptides obtained from azurin preferentially enter cancer cells

Cancer Research
Brad N TaylorTapas K Das Gupta

Abstract

Azurin, a member of the cupredoxin family of copper containing redox proteins, preferentially penetrates human cancer cells and exerts cytostatic and cytotoxic (apoptotic) effects with no apparent activity on normal cells. Amino acids 50 to 77 (p28) of azurin seem responsible for cellular penetration and at least part of the antiproliferative, proapoptotic activity of azurin against a number of solid tumor cell lines. We show by confocal microscopy and fluorescence-activated cell sorting that amino acids 50 to 67 (p18) are a minimal motif (protein transduction domain) responsible for the preferential entry of azurin into human cancer cells. A combination of inhibitors that interfere with discrete steps of the endocytotic process and antibodies for caveolae and Golgi-mediated transport revealed that these amphipathic, alpha-helical peptides are unique. Unlike the cationic cell-penetrating peptides, alpha-helical antennapedia-like, or VP22 type peptides, p18 and p28 are not bound by cell membrane glycosaminoglycans and preferentially penetrate cancer cells via endocytotic, caveosome-directed, and caveosome-independent pathways. Once internalized, p28, but not p18, inhibits cancer cell proliferation initially through a cytostatic ...Continue Reading

References

May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·R A CrucianiO Colamonici
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·D TranL Orci
Mar 1, 1988·The Journal of Cell Biology·K R GehlsenE Ruoslahti
Aug 2, 1996·Journal of Medicinal Chemistry·M M JavadpourM L McLaughlin
Jun 1, 1997·Nature Biotechnology·R PasqualiniE Ruoslahti
Oct 30, 2001·The Journal of Biological Chemistry·Leslie H KondejewskiRobert S Hodges
Sep 20, 2002·Journal of Virology·Sara B Sieczkarski, Gary R Whittaker
Nov 2, 2002·The Journal of Biological Chemistry·Jean Philippe RichardBernard Lebleu
Dec 25, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Siobhan M CashmanRajendra Kumar-Singh
Oct 1, 2003·The Journal of Biological Chemistry·Terra B PotockySamuel H Gellman
Nov 18, 2003·Traffic·Robert G Parton, Ayanthi A Richards
Mar 3, 2004·Biochemistry·Stephen M Fuchs, Ronald T Raines
Mar 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Tohru YamadaAnanda M Chakrabarty
Jun 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Pirjo LaakkonenErkki Ruoslahti
Jul 29, 2004·Current Pharmaceutical Design·Carola Leuschner, William Hansel
Oct 2, 2004·Science·Emily A PartridgeJames W Dennis
Jul 20, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Di-Sheng YangFen-Fen Ge
Sep 3, 2005·Analytical Biochemistry·Külliki SaarUlo Langel
Sep 13, 2005·Cellular Microbiology·Tohru YamadaAnanda M Chakrabarty
Oct 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Helge EwersAri Helenius
Aug 11, 2006·The Journal of Gene Medicine·Samir El-AndaloussiUlo Langel
Dec 19, 2006·The Journal of Clinical Investigation·Galina A GusarovaRobert H Costa
Jul 20, 2007·Biochemical Society Transactions·J Enbäck, P Laakkonen
Jul 20, 2007·Biochemical Society Transactions·A Melnick
Sep 18, 2007·Chembiochem : a European Journal of Chemical Biology·Gaetano D ManettoCarmelo La Rosa
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Florian HohlaGabor Halmos
Feb 1, 2008·Nature Methods·Yuriy SharikovIgor F Tsigelny

❮ Previous
Next ❯

Citations

May 7, 2013·Applied Microbiology and Biotechnology·Nuno BernardesArsenio M Fialho
Mar 31, 2009·Applied and Environmental Microbiology·Anneke KuipersGert N Moll
Dec 14, 2011·International Journal of Nanomedicine·Anna Rita BizzarriSalvatore Cannistraro
Mar 31, 2012·ISRN Neurology·Arsenio M FialhoAnanda M Chakrabarty
Aug 13, 2011·Expert Opinion on Investigational Drugs·Alexandre PereiraIrina Kerkis
Apr 3, 2012·Drug Discovery Today·Francesca Milletti
Mar 5, 2016·Molecular Pharmaceutics·Ran PanP Chen
Nov 15, 2011·Biotechnology Journal·Jae-Hun LeeByung-Gee Kim
May 18, 2011·Journal of Molecular Recognition : JMR·Fabio DomeniciSalvatore Cannistraro
Nov 1, 2011·Journal of Molecular Recognition : JMR·Simona SantiniSalvatore Cannistraro
Aug 13, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Siegmund Reissmann
Feb 26, 2015·Bioengineered·Wataru HashimotoAnanda M Chakrabarty
Feb 7, 2013·Biochemical and Biophysical Research Communications·Amir Abbas MokhtariehMyung Kyu Lee
May 12, 2016·Advanced Biomedical Research·Meysam SoleimaniAli Jahanian-Najafabadi
Feb 18, 2011·Bioengineered Bugs·Ananda M Chakrabarty
May 31, 2014·Bioengineered·Ananda M ChakrabartyArsenio M Fialho
Feb 11, 2014·The International Journal of Biochemistry & Cell Biology·Nuno BernardesArsenio M Fialho
Apr 9, 2015·Therapeutic Delivery·Nele Van DesselNeil S Forbes
Dec 3, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Feihu WangFang Jin
Oct 16, 2015·PloS One·Sofie StalmansBart De Spiegeleer
May 14, 2010·Pharmaceuticals·Irene MartínErnest Giralt
Feb 26, 2016·International Journal of Molecular Sciences·Ana DincaMichael T Chin
Oct 24, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sara Neves-CoelhoMiguel A R B Castanho
Sep 30, 2017·Protein Science : a Publication of the Protein Society·Meng GaoYongqi Huang
May 10, 2018·Angewandte Chemie·Leila Peraro, Joshua A Kritzer
Jun 6, 2013·British Journal of Cancer·T YamadaC W Beattie
Jul 30, 2020·Future Medicinal Chemistry·Annarita FalangaStefania Galdiero
Mar 3, 2011·Chembiochem : a European Journal of Chemical Biology·Irene MartínErnest Giralt
Jan 25, 2020·Beilstein Journal of Nanotechnology·Ivana Ruseska, Andreas Zimmer
Aug 28, 2020·Frontiers in Oncology·Atieh YaghoubiSaman Soleimanpour
Mar 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Justine Habault, Jean-Luc Poyet
Mar 30, 2020·AMB Express·Manar MansourKhaled Abou-Aisha

❮ Previous
Next ❯

Related Concepts

Related Feeds

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.

© 2021 Meta ULC. All rights reserved