Growth hormone - releasing hormone antagonists induce autophagy in cancer cells

Madan Sigdel1, Saikat Fakir1, Md Matiur Rahman Sarker1

  • 1School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, USA.

Insights

Growth hormone-releasing hormone antagonists (GHRHAnt) were found to induce autophagy in cancer cells expressing GHRH receptors. This suggests autophagy may mediate the anti-cancer effects of GHRHAnt.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Growth hormone-releasing hormone antagonists (GHRHAnt) are investigated for cancer suppression.
  • GHRHAnt exhibit anti-inflammatory and anti-oxidative properties, but underlying mechanisms are unclear.
  • Autophagy is a cellular process implicated in cancer development and treatment.

Purpose of the Study:

  • To investigate the effect of GHRHAnt JV-1-36 on autophagy in cancer cells.
  • To determine if GHRH receptor expression influences the response to GHRHAnt.

Main Methods:

  • Treatment of GHRH receptor-expressing cancer cells (MDA-MB-468, A549) and non-expressing cells (MCF-7) with GHRHAnt JV-1-36.
  • Evaluation of autophagy markers, including autophagy-related proteins (ATG) 5, 3, 7, and 16L1, via expression level analysis.

Main Results:

  • GHRHAnt JV-1-36 treatment induced autophagy in MDA-MB-468 and A549 cells.
  • Elevated expression of ATG-5, ATG-3, ATG-7, and ATG-16L1 was observed in response to GHRHAnt.
  • MCF-7 cells, lacking GHRH receptors, did not exhibit an autophagic response to GHRHAnt.

Conclusions:

  • GHRHAnt may exert beneficial effects in cancer treatment by inducing autophagy.
  • GHRH receptor expression is critical for mediating the autophagic response to GHRHAnt.
  • Further research is needed to elucidate the precise molecular mechanisms involved.

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.8K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.3K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.7K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K