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Published on: June 30, 2023
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.
Abstract:
GHRH antagonists (GHRHAnt) were developed to suppress cancers and have been associated with robust anti-inflammatory and anti-oxidative activities. The mechanisms involved in those effects are not completely understood. MDA-MB-468 and A549 cancer cells, which express GHRH receptors, were treated with GHRHAnt JV-1-36, to evaluate the effects of that compound in autophagy. JV-1-36 induces autophagy in MDA-MB-468 and A549 cells since exposure to the aforementioned peptide elevated the expression levels of the autophagy-related protein (ATG) - 5, ATG - 3, ATG - 7, and ATG-16L1. In contrast, MCF-7 cells - which do not express GHRH receptors - did not respond to GHRHAnt. Our findings suggest that the beneficial effects of GHRHAnt in cancers may involve autophagy. Further studies will attempt to delineate the underlying mechanisms.
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.
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