Antitumor effects of analogs of LH-RH and somatostatin: Experimental and clinical studies

Adenocarcinoma Cells Are Targeted by the New GnRH-PE66 Chimeric Toxin through Specific Gonadotropin-releasing Hormone Binding Sites

“…moiety is of prime importance, particularly when the full toxic dose is not provided and the targeting portion has a contributive effect on the tumor. Most likely this does not apply to the present case, as GnRH exhibits antitumor activity against a variety of cancer cells (1,34). If this is the case, then the effect of our chimeric toxin could be an additive one.…”

“…Gonadotropin-releasing hormone (GnRH) 1 is a decapeptide that is normally synthesized by the hypothalamic neurons and secreted into the hypophysioportal circulation via portal vessels. It is synthesized as a larger peptide and matures through proteolytic processing and amidation at its C-terminal glycine.…”

“…The involvement of GnRH has been demonstrated in several carcinomas (1). GnRH-specific binding sites have been reported in some solid tumors, as well as in established cell lines (2)(3)(4)(5)(6), although the functional role of these binding sites in human neoplasms remains obscure.…”

“…: 972-2-6757465 (or 6758146); Fax: 972-2-6415848; E-mail: hayalg@md2.huji.ac.il. 1 The abbreviations used are: GnRH, gonadotropin-releasing hormone; PE, Pseudomonas exotoxin; LH, luteinizing hormone; LHRH, luteinizing hormone-releasing hormone; PBS, phosphate-buffered saline; PAGE, polyacrylamide gel electrophoresis.…”

Histidine7.36(305) in the conserved peptide receptor activation domain of the gonadotropin releasing hormone receptor couples peptide binding and receptor activation

“…GnRH analogs have been used for treatment of a range of reproductive hormonedependent disorders, including various forms of infertility as well as hypertrophy and cancers of reproductive tissues (Betz et al, 2008;Kim et al, 2009;Labrie et al, 2005;Millar et al, 2004;Samant et al, 2005;Schally et al, 1990). Many peptide ligands, including chemokines and endogenous opioids, interact with their receptors via two sites, one that determines binding affinity and a second site that induces receptor activation (Choi et al, 2012;Filizola and Devi, 2013;Flanagan, 2014;Granier et al, 2012;Pease and Horuk, 2012;Portoghese, 1992).…”