Title:Angiotensin-(1-7): A Peptide Hormone with Anti-Cancer Activity
Volume: 21
Issue: 21
Author(s): P.E. Gallagher, A.L. Arter, G. Deng and E.A. Tallant
Affiliation:
Keywords:
Angiogenesis, angiotensin receptor, angiotensin-(1-7), cancer associated fibrosis, cancer, kinase, mas, osteoclastogenesis,
phosphatase, placental growth factor, tumor microenvironment, vascular endothelial growth factor.
Abstract: The development of peptides as therapeutic agents has progressed such that these small molecules of less than
fifty amino acids are currently in use for the treatment of a variety of pathologies. This review focuses on the pre-clinical
studies and clinical trials assessing the anti-cancer properties of angiotensin-(1-7) [Ang-(1-7)], an endogenous heptapeptide
hormone of the renin-angiotensin system. Ang-(1-7) mediates biological responses by activating mas, a unique G protein-
coupled receptor, thereby providing specific targeted actions when used as a therapeutic agent. Studies in in vitro as
well as in vivo mouse models demonstrated that the heptapeptide hormone reduced proliferation of human cancer cells
and xenograft tumors. This attenuation was concomitant with decreased angiogenesis, cancer associated fibrosis, osteoclastogenesis,
tumor-induced inflammation and metastasis as well as altered regulation of growth promoting cellular signaling
pathways. In three clinical trials, Ang-(1-7) was well tolerated with limited toxic or quality-of-life side effects and
showed clinical benefit in cancer patients with solid tumors. Taken together, these studies suggest that Ang-(1-7) may
serve as a first-in-class peptide chemotherapeutic agent, reducing cancer growth and metastases by pleiotrophic mechanisms
as well as targeting the tumor microenvironment.
