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

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.