Unveiling the Intricacies of Monoamine Oxidase-A (MAO-A) Inhibition in Colorectal Cancer: Computational Systems Biology, Expression Patterns, and the Anticancer Therapeutic Potential.

Autor:	Bardaweel SK; Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan., Al-Salamat H; Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan., Hajjo R; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman - 11733, Jordan.; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.; Board Member, Jordan CDC, Amman - 11183, Jordan., Sabbah D; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman - 11733, Jordan., Almutairi S; Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2024 Aug 09; Vol. 9 (33), pp. 35703-35717. Date of Electronic Publication: 2024 Aug 09 (Print Publication: 2024).
DOI:	10.1021/acsomega.4c04100
Abstrakt:	Colorectal cancer (CRC) remains a significant health burden globally, necessitating a deeper understanding of its molecular intricacies for effective therapeutic interventions. Elevated monoamine oxidase-A (MAO-A) expression has been consistently observed in CRC tissues, correlating with advanced disease stages and a poorer prognosis. This research explores the systems biology effects of MAO-A inhibition with small molecule inhibitor clorgyline regarding CRC. The applied systems biology approach starts with a chemocentric informatics approach to derive high-confidence hypotheses regarding the antiproliferative effects of MAO-A inhibitors and ends with experimental validation. Our computational results emphasized the anticancer effects of MAO-A inhibition and the chemogenomics similarities between clorgyline and structurally diverse groups of apoptosis inducers in addition to highlighting apoptotic, DNA-damage, and microRNAs in cancer pathways. Experimental validation results revealed that MAO inhibition results in antiproliferative antimigratory activities in addition to synergistic effects with doxorubicin. Moreover, the results demonstrated a putative role of MAO-A inhibition in commencing CRC cellular death by potentially mediating the induction of apoptosis. Competing Interests: The authors declare no competing financial interest. (© 2024 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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