Abstract 1318: Cytotoxic effect of plant-based alkaloid veratridine on patient-derived colorectal cancer spheroid cells

Abstract Colorectal cancer (CRC) causes approximately 900, 000 deaths annually worldwide. The survival rate for patients diagnosed with localized CRC is 90 percent; however, once the cancer metastasizes or spreads to other parts of the body, the five-year survival rate drops to a dismal 15%. There is a clear need for a new generation of targeted therapies that can safely and efficiently target the metastatic features of CRC cells. Our lab has shown that veratridine (VTD), a lipid-soluble plant alkaloid, can enhance the expression of a ubiquitin-like protein called UBXN2A as a colon-specific tumor suppressor protein. UBXN2A binds and negatively regulates the Rictor protein, a key member of the mTORC2 signaling pathway. This results in suppression of mTORC2-AKT’s downstream signaling pathway in cancer cells. We hypothesize that the VTD-UBXN2A axis decreases migration in human CRC tumors. Human colon cancer cells and patient-derived xenograft cell lines in 2D and 3D spheroid forms were used to complete this project. Real-time cell migration and invasion analysis using xCELLigence technology and Cytation 1 cell imaging system revealed the VTD-UBXN2A axis can suppress metastatic characteristics of CRC cells, including cell proliferation and migration. Small molecule targeted compounds have been successfully developed in clinical medicine to prolong the survival time of patients with advanced tumors. This ongoing study will provide detailed insight into the therapeutic efficacy of a potential targeted therapy to safely and effectively target CRC cells while normal cells can remain intact. Citation Format: Kate Schraufnagel, Morgan Eikanger, Khosrow Rezvani. Cytotoxic effect of plant-based alkaloid veratridine on patient-derived colorectal cancer spheroid cells [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 1318.