GHRH antagonist peptide JV-1-36 induces autophagy in cancer cells through a receptor-dependent mechanism | Research

The takeaway

The GHRH antagonist peptide JV-1-36 induces autophagy in breast (MDA-MB-468) and lung (A549) cancer cells by elevating autophagy-related proteins ATG-5, ATG-3, ATG-7, and ATG-16L1, but only in cells expressing GHRH receptors.

Receptor-dependent autophagy
GHRH antagonist JV-1-36 induces autophagy only in cancer cells expressing GHRH receptors, confirming a specific peptide-mediated mechanism

What the researchers found

JV-1-36 elevated ATG-5, ATG-3, ATG-7, ATG-16L1 in GHRH receptor-positive MDA-MB-468 and A549 cells. No effect in GHRH receptor-negative MCF-7 cells. Confirms receptor-dependent autophagy induction.

Why it matters

GHRH antagonists are anti-cancer peptides with known anti-inflammatory and anti-oxidative effects. Discovering that autophagy is another mechanism adds to understanding of their multi-modal anti-cancer activity.

How the study worked

In vitro treatment of breast (MDA-MB-468, MCF-7) and lung (A549) cancer cell lines with GHRH antagonist JV-1-36. GHRH receptor expression confirmed. Autophagy marker protein levels assessed.

What this study cannot tell us

In vitro only. Limited to 3 cell lines. Functional significance of autophagy (pro-death vs pro-survival) not determined. No in vivo validation.

How to read the evidence

In vitro study with appropriate receptor-negative control. Provides mechanistic insight but limited scope.

When this study was published

Published in 2025.

The bigger picture

GHRH antagonists represent a peptide-based approach to cancer treatment distinct from GLP-1 drugs. Understanding that they induce autophagy provides new insight into their mechanism and could guide combination strategies.

Questions still open

Is GHRH antagonist-induced autophagy pro-death or pro-survival for cancer cells?
Could combining GHRH antagonists with autophagy modulators enhance anti-cancer effects?
Do GHRH antagonists induce autophagy in non-cancerous cells?

Common questions

What is GHRH and why block it in cancer?

Growth hormone-releasing hormone (GHRH) stimulates growth hormone release but also promotes cancer cell growth through receptors expressed on many tumors. GHRH antagonist peptides block these receptors, suppressing tumor growth. This study found they also trigger autophagy—a cellular cleanup process that may contribute to cancer cell death.

What is autophagy in cancer?

Autophagy is a process where cells digest and recycle their own damaged components. In cancer, it can be either protective (helping cancer cells survive stress) or destructive (causing cell death). Understanding which role GHRH antagonist-induced autophagy plays is crucial for developing effective treatments.

Read the original research

Growth hormone - releasing hormone antagonists induce autophagy in cancer cells.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 82, 101668

View on PubMed ↗Publisher’s paper ↗

Citation

Sigdel, Madan; Fakir, Saikat; Sarker, Md Matiur Rahman; Barabutis, Nektarios. (2025). Growth hormone - releasing hormone antagonists induce autophagy in cancer cells.. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 82, 101668. https://doi.org/10.1016/j.ghir.2025.101668