This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, B. N. Articles by Das Gupta, T. K. Search for Related Content PubMed PubMed Citation Articles by Taylor, B. N. Articles by Das Gupta, T. K.

Noncationic Peptides Obtained From Azurin Preferentially Enter Cancer Cells

Departments of ¹ Surgical Oncology and ² Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois

Requests for reprints: Tapas K. Das Gupta, 840 South Wood Street, Chicago, IL 60612. Phone: 312-996-6134; Fax: 312-996-9365; E-mail: TKDG{at}uic.edu.

Key Words: azurin • cancer cell • cytostatic

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, -helical peptides are unique. Unlike the cationic cell-penetrating peptides, -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 mechanism. These observations suggest the azurin fragments, p18 and p28, account for the preferential entry of azurin into human cancer cells and a significant amount of the antiproliferative activity of azurin on human cancer cells, respectively. [Cancer Res 2009;69(2):537–46]

This article has been cited by other articles:

				T. Yamada, R. R. Mehta, F. Lekmine, K. Christov, M. L. King, D. Majumdar, A. Shilkaitis, A. Green, L. Bratescu, C. W. Beattie, et al. A peptide fragment of azurin induces a p53-mediated cell cycle arrest in human breast cancer cells Mol. Cancer Ther., October 1, 2009; 8(10): 2947 - 2958. [Abstract] [Full Text] [PDF]

				A. Kuipers, R. Rink, and G. N. Moll Translocation of a Thioether-Bridged Azurin Peptide Fragment via the Sec Pathway in Lactococcus lactis Appl. Envir. Microbiol., June 1, 2009; 75(11): 3800 - 3802. [Abstract] [Full Text] [PDF]