Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy

Chan, Lai Yue, Craik, David J., and Daly, Norelle L. (2016) Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy. Scientific Reports, 6. 35347. pp. 1-13.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview
View at Publisher Website: http://dx.doi.org/10.1038/srep35347
 
25
55


Abstract

Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers.

Item ID: 49213
Item Type: Article (Research - C1)
ISSN: 2045-2322
Keywords: peptides, tumour angiogenesis
Additional Information:

© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Funders: Australian Research Council (ARC), National Health and Medical Research Council (NHMRC)
Projects and Grants: ARC LF150100146 & FF110100226, NHMRC APP1028509
Date Deposited: 13 Jun 2017 02:20
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111205 Chemotherapy @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
Downloads: Total: 55
Last 12 Months: 26
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page