Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wild-type p53 and decrease in p21 and mutant p53 proteins.
Stangelberger. Anton A; Schally. Andrew V AV; Rick. Ferenc G FG; Varga. Jozsef L JL; Baker. Benjamin B; Zarandi. Marta M; Halmos. Gabor G
Key Findings
- GHRH antagonist MZ‑J‑7‑138 significantly inhibited growth of three prostate‑cancer xenografts in mice
- Treatment lowered mutant p53 and p21 levels in PC‑3 and DU‑145 tumors, while wild‑type p53 rose in MDA‑PCa‑2b tumors when combined with the LHRH antagonist Cetrorelix
- Both GHRH and LHRH receptors are present in these tumors, and combining antagonists enhanced anti‑tumor effects
Practical Outcomes
- For the biohacker community, the study hints that blocking GHRH signaling might influence cancer‑related pathways, but it provides no actionable protocol for sermorelin use. There’s no evidence that taking sermorelin will give these anti‑cancer benefits, and the findings are limited to animal models.
Summary
In mouse studies, a drug that blocks the growth‑hormone‑releasing hormone (GHRH) slowed the growth of prostate cancer tumors and changed key cancer‑related proteins, especially p53. Adding another hormone blocker (Cetrorelix) made the effect stronger. The work doesn’t involve sermorelin (a GHRH‑activating peptide) and offers no direct guidance for human use.
Abstract
The tumor suppressor gene p53 is implicated in cell cycle control and apoptosis. Antagonists of growth hormone-releasing hormone (GHRH) have been shown to inhibit human experimental prostate cancers. We investigated the involvement of p53 apoptotic pathways in this effect. Nude mice bearing xenografted PC-3, DU-145, and MDA-PCa-2b human prostate cancer lines were treated with a new potent GHRH antagonist MZ-J-7-138. To determine whether tumor inhibition by MZ-J-7-138 involves apoptotic mechanisms such as p53 and p21, we evaluated by Western Blot the expression of mutant mt-p53 in PC-3 and DU-145 and of wild type (wt-p53) in MDA-PCa-2b prostate cancers as well as p21. MZ-J-7-138 significantly inhibited the growth of PC-3, DU-145, and MDA-PCa-2b xenografts in nude mice. Androgen deprivation with the LHRH antagonist Cetrorelix enhanced the anti-proliferative effect of GHRH antagonist MZ-J-7-138 on MDA-PCa-2b tumors. The expression of mutant (mt-p53) and p21 protein in PC-3 and DU-145 tumors was significantly decreased by treatment with MZ-J-7-138, whereas wild type wt-p53 expression in MDA-PCA-2b tumors was up regulated by treatment with Cetrorelix. All three models investigated expressed specific, high affinity GHRH receptors. Our findings indicate that the anti-proliferative effects of GHRH antagonist MZ-J-7-138 and LHRH antagonist Cetrorelix on prostate cancers involve p53 and p21 signaling.
Study Information
pubmed
2011
2011-07-27T00:00:00.000Z
10.1002/pros.21458
33
57