title: Anti-Tumoral Activity of a Short Decapeptide Fragment of the Alzheimer's Abeta Peptide.
abstract: The inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Abeta peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell proliferation as determined by Ki67 immunostaining were observed following treatment with the Abeta fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Abeta derivative peptide may constitute a new antitumoral agent.
authors.affiliation: The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paris
authors.forename: Nikunj
authors.initials: N
authors.lastname: Patel
authors.forename: Nowell J
authors.initials: NJ
authors.lastname: Ganey
authors.forename: Vincent
authors.initials: V
authors.lastname: Laporte
authors.forename: Amita
authors.initials: A
authors.lastname: Quadros
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullan
references.citation: Neurol Res. 2003 Sep;25(6):642-51
references.pmid: 14503019
references.citation: AJNR Am J Neuroradiol. 2007 Apr;28(4):731-6
references.pmid: 17416830
references.citation: Trends Neurosci. 2005 Apr;28(4):202-8
references.pmid: 15808355
references.citation: Angiogenesis. 2004;7(1):75-85
references.pmid: 15302999
references.citation: Neurobiol Aging. 2008 Jan;29(1):1-11
references.pmid: 17055615
references.citation: Neurology. 2005 Mar 8;64(5):895-8
references.pmid: 15753432
references.citation: Curr Alzheimer Res. 2007 Apr;4(2):191-7
references.pmid: 17430246
references.citation: Lancet. 1992 Jan 11;339(8785):71-85
references.pmid: 1345869
references.citation: Neurol Res. 2005 Dec;27(8):869-81
references.pmid: 16354549
references.citation: Neurosci Lett. 2007 Nov 27;428(2-3):53-8
references.pmid: 17964720
references.citation: J Clin Pathol. 2004 Jul;57(7):675-81
references.pmid: 15220356
references.citation: Pharmacol Rev. 2001 Mar;53(1):25-71
references.pmid: 11171938
references.citation: J Am Geriatr Soc. 1999 Feb;47(2):189-95
references.pmid: 9988290
references.citation: Cell Death Differ. 2006 Jul;13(7):1088-96
references.pmid: 16410806
references.citation: J Natl Cancer Inst. 2005 Nov 16;97(22):1652-62
references.pmid: 16288118
references.citation: J Am Geriatr Soc. 1992 Oct;40(10):1075
references.pmid: 1401685
references.citation: J Am Geriatr Soc. 1991 Aug;39(8):840
references.pmid: 2071819
references.citation: Nat Rev Mol Cell Biol. 2007 Feb;8(2):101-12
references.pmid: 17245412
references.citation: J Natl Cancer Inst. 1995 May 3;87(9):645-51
references.pmid: 7752269
references.citation: Arch Neurol. 2005 May;62(5):779-84
references.pmid: 15883266
references.citation: Mech Ageing Dev. 2009 Jan-Feb;130(1-2):98-104
references.pmid: 18452970
references.citation: J Natl Cancer Inst. 2007 Jan 17;99(2):167-70
references.pmid: 17228000
references.citation: Nat Med. 2005 Sep;11(9):959-65
references.pmid: 16116430
references.citation: J Alzheimers Dis. 2007 Mar;11(1):33-44
references.pmid: 17361033
references.citation: Neurosci Lett. 2004 Aug 5;366(1):80-5
references.pmid: 15265595
references.citation: Amyloid. 2008 Mar;15(1):5-19
references.pmid: 18266117
references.citation: Neurology. 2008 Jul 8;71(2):85-92
references.pmid: 18509095
references.citation: Exp Cell Res. 2009 Feb 1;315(3):385-95
references.pmid: 19061884
references.citation: J Endocrinol. 1979 Dec;83(3):401-8
references.pmid: 536670
references.citation: Endocrinology. 2007 Mar;148(3):1171-80
references.pmid: 17138652
references.citation: Brain Res Mol Brain Res. 2005 May 20;136(1-2):212-30
references.pmid: 15893605
references.citation: Mol Med. 2009 Mar-Apr;15(3-4):95-100
references.pmid: 19081767
references.citation: Breast Cancer Res Treat. 1998;51(3):227-38
references.pmid: 10068081
references.citation: Baillieres Clin Endocrinol Metab. 1990 Mar;4(1):67-84
references.pmid: 1975167
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3587-92
references.pmid: 18305170