Deciphering angiotensin converting enzyme 2 (ACE2) inhibition dynamics: Carnosine's modulatory role in breast cancer proliferation – A clinical sciences perspective

Abstract

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.

Keywords

• Carnosine
• Angiotensin-converting enzyme 2 (ACE2)
• Inhibitor
• Breast cancer
• Triple negative
• Luminal