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Deciphering angiotensin converting enzyme 2 (ACE2) inhibition dynamics: Carnosine's modulatory role in breast cancer
Sarah A Melhem1, Loai M Saadah1, Zeena S Attallah1
1Department of Clinical Pharmacy, Faculty of Pharmacy, Applied Science Private University. Amman, Jordan.
Background:
Angiotensin-converting enzyme 2 (ACE2) is a pivotal molecular nexus linking novel coronavirus disease to breast cancer. In-silico investigations have repurposed carnosine for both these conditions based on its potential ACE2 inhibitory properties.
Methods:
Utilizing an ACE2 inhibitor screening kit, we determined the inhibitory range of carnosine doses. Subsequently, we examined the effect of carnosine on ACE2 expression in supernatants from various breast cancer cell lines (MCF-7, MDA-MB-231, and EMT-6). Additionally, we compared ACE2 activity in cell line pellets with and without carnosine and a putative ACE2 activator using a fluorometric activity assay kit. Finally, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay across overlapping concentrations.
Results:
Carnosine exhibited dose-dependent ACE2 inhibition within the 100-300 mM range. ACE2 expression significantly diminished after exposure to carnosine for 2 and 24 h in MDA-MB-231 and MCF-7 cell lines, respectively. MTT assay unveiled notable antiproliferative effects in MDA-MB-231 (50 % survival at approximately 265 mM) and EMT-6 cell lines (unquantifiable 50 % survival dose). Conversely, the MCF-7 cell line displayed a modest increase in proliferation (Effective concentration 50-186 mM, ∼40 % increased survival).
Conclusion:
This pioneering study delineates evident dose-dependent ACE2 inhibition by carnosine. Moreover, it unveils the modulatory impact of this ACE2 inhibitor in breast cancer cell lines. Carnosine demonstrated a significant antiproliferative effect on aggressive cell lines while sparing luminal cell lines from substantial toxic or proliferative effects.
Insights
Carnosine inhibits angiotensin-converting enzyme 2 (ACE2) in a dose-dependent manner, impacting breast cancer cell lines. This study shows carnosine
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Angiotensin-converting enzyme 2 (ACE2) is a key molecular target linking viral infections to breast cancer.
- In silico studies suggest carnosine as a potential therapeutic agent due to its ACE2 inhibitory properties.
Purpose of the Study:
- To investigate carnosine's dose-dependent ACE2 inhibition.
- To evaluate carnosine's effects on ACE2 expression and activity in breast cancer cell lines.
- To assess carnosine's impact on breast cancer cell proliferation.
Main Methods:
- ACE2 inhibitor screening kit used to determine carnosine's inhibitory range.
- Fluorometric assay to measure ACE2 expression and activity in MCF-7, MDA-MB-231, and EMT-6 cell lines.
- MTT assay to evaluate antiproliferative effects of carnosine.
Main Results:
- Carnosine demonstrated dose-dependent ACE2 inhibition between 100-300 mM.
- ACE2 expression decreased in MDA-MB-231 and MCF-7 cells after carnosine exposure.
- Carnosine exhibited antiproliferative effects on MDA-MB-231 and EMT-6 cells, but increased proliferation in MCF-7 cells.
Conclusions:
- Carnosine effectively inhibits ACE2 in a dose-dependent manner.
- Carnosine modulates ACE2 activity and proliferation in breast cancer cell lines.
- Carnosine shows potential as an antiproliferative agent for aggressive breast cancer subtypes.
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