Abstract 1323: Monoamine oxidase B: a potential therapeutic target for colorectal cancer

Background: Colorectal cancer (CRC) is one of the most prevalent cancers globally. Tumor recurrence occurs in approximately 30% of late-stage patients largely due to distant metastases. Angiogenesis plays a pivotal role in CRC progression. Recent studies have reported elevated expression levels of monoamine oxidases (MAO A and MAO B) in several cancers. However, the specific roles of MAO B in CRC progression and prognosis remain largely unexplored. Our previous work demonstrated improved survival outcomes and therapeutic efficacy of MAO A inhibitors in CRC preclinical models. In-silico analyses reveal that MAO B expression is significantly elevated in CRC tissues compared to normal tissues, correlating with higher recurrence rates and mesenchymal-type gene expression patterns. Objective: This study investigates the therapeutic efficacy of MAO B inhibitors- deprenyl, rasagiline, and safinamide in CRC cell lines, assessing their potential to reduce metastasis through epithelial-mesenchymal transition (EMT) reversal and to study their role in modulating angiogenesis. Methods: We studied the effects of MAO B Inhibitors on cell viability of CRC cell lines HCT116 and HT29 following treatment by MTS assay. Changes in EMT-related genes were analyzed at transcription and translation level through RT-qPCR, western blot, and immunocytochemistry (ICC). Scratch assays were used to evaluate the metastatic potential of treated cells, and RT-qPCR quantified angiogenesis-related markers. Results: Our findings confirm that MAO B expression is significantly elevated in CRC cell lines-HCT116 and HT29 compared to normal colon cell - FHC. Treatment with MAO B inhibitors effectively reduced MAO B expression in CRC cells while showing no cytotoxic effect to normal colon cells with the same dose treatment. EMT marker analysis revealed a reduction in mesenchymal characteristics and an increase in epithelial markers, indicating a shift toward less metastatic phenotypes. Scratch assays demonstrated a decrease in metastatic potential in treated cancer cells, further supported by RT-qPCR results showing reduced expression of metastatic markers (N-cadherin, TWIST and Snail) and increased expression of epithelial markers (E-cadherin). We also observed a significant decrease in angiogenesis-related markers (VEGFR2) at transcription level. Western blot and ICC validated these findings at the protein level. Notably, HT29 cells (BRAF-mutant) exhibited greater sensitivity to MAO B inhibitors, showing better reduction in metastatic and angiogenic markers compared to HCT116 cells. Conclusion: MAO B is a promising biomarker and therapeutic target for CRC. MAO B inhibitors effectively reduce metastatic and angiogenic potential in CRC cells, providing a novel approach for CRC treatment. These findings warrant further investigation to establish their clinical applicability and therapeutic potential. Citation Format: Unnati Hemant Shah, Shivani Soni, Lesly Torres-Gonzalez, Joshua Millstein, Pooja Mittal, Francesca Battaglin, Karam Ashouri, Sandra Algaze, Priya Jayachandran, Wu Zhang, Jean C. Shih, Heinz-Josef Lenz. Monoamine oxidase B: a potential therapeutic target for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1323.