Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines.
Cassoni. P P; Papotti. M M; Ghè. C C; Catapano. F F; Sapino. A A; Graziani. A A; Deghenghi. R R; Reissmann. T T; Ghigo. E E; Muccioli. G G
Key Findings
- Specific growth‑hormone‑secretagogue (GHS) binding sites were identified in human breast cancer tissues, especially well‑differentiated tumors.
- Hexarelin, ghrelin, and other GHS compounds competed with a radiolabeled ligand, confirming they bind these receptors.
- At concentrations near their binding affinity, hexarelin and similar compounds significantly reduced proliferation of breast cancer cell lines in vitro.
Practical Outcomes
- While the study hints that hexarelin might have anti‑cancer effects, there’s no human data, dosing guidance, or safety information. Biohackers should not add hexarelin to longevity or performance regimens based on this work alone.
Summary
Scientists discovered that hexarelin and related molecules stick to special receptors on breast cancer cells and can slow the cells' growth in lab dishes, but this is an early‑stage finding and not a proven treatment for people.
Abstract
The family of GH secretagogues (GHS) includes synthetic peptidyl (hexarelin) and nonpeptidyl (MK-0677) molecules possessing specific receptors in the pituitary and central nervous system as well as in peripheral tissues, including the heart and some endocrine organs. A gastric-derived peptide, named ghrelin, has recently been proposed as the natural ligand of the GHS receptors (GHS-Rs). The presence of specific GHS-Rs has now been investigated in nontumoral and neoplastic human breast tissue using a radioiodinated peptidyl GHS ([(125)I]-Tyr-Ala-hexarelin) as ligand. Specific binding sites for GHS were detected in membranes from several types of breast carcinomas, whereas a negligible binding was found in fibroadenomas and mammary parenchyma. The highest binding activity was found in well-differentiated (G1) invasive breast carcinomas and was progressively reduced in moderately (G2) to poorly (G3) differentiated tumors. [(125)I]-Tyr-Ala-hexarelin bound to tumor membranes was displaced by different unlabeled GHS such as hexarelin, Tyr-Ala-hexarelin, human ghrelin, and MK-0677 as well as by desoctanoyl-ghrelin and hexarelin derivative EP-80317, which are devoid of GH-releasing properties in vivo. In contrast, no competition was seen between radiolabeled Tyr-Ala-hexarelin and some peptides (CRF and insulin-like growth factor I) structurally and functionally unrelated to hexarelin or when GHRH and SRIF were tested in the displacement studies. The presence of specific GHS binding sites was also demonstrated in three different human breast carcinoma cell lines (MCF7, T47D, and MDA-MB231), in which, surprisingly, no messenger RNA for GHS-R1a was demonstrated by RT-PCR. In these cell lines, ghrelin (as well as hexarelin, MK-0677, EP-80317, and even desoctanoyl ghrelin) caused a significant inhibition of cell proliferation at concentrations close to their binding affinity. In conclusion, this study provides the first demonstration of specific GHS binding sites, other than GHS-R1, in breast cancer. These receptors probably mediate growth inhibitory effects on breast carcinoma cells in vitro.
Study Information
pubmed
2001
10.1210/jcem.86.4.7402