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Document Type

Poster

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Publication Date

4-2021

Keywords

veratridine, plant-derived, anti-metastatic, colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and is the second leading cause of cancer-related deaths for both men and women in the United States. CRC causes approximately 49,200 deaths annually. Metastasis is a common feature in many CRC tumors and is largely responsible for the mortality and morbidity of patients. A five-year survival rate of 91% for localized disease can be attributed to the success of surgical resection, but this rate drops to approximately 12% for patients who are diagnosed with disseminated form of the disease due to the lack of effective therapies. There is a clear need to develop safer and more effective targeted therapies that are capable of significantly decreasing the high mortality rates associated with the metastatic form of human colorectal cancer. This study focuses on Veratridine (VTD), a lipid-soluble alkaloid extracted from Liliaceae plants. VTD transcriptionally increases a ubiquitin-like molecule, UBXN2A, that functions as a tumor suppressor protein in colorectal cancer (CRC). In this study, we used a set of in vitro experiments to show VTD-dependent induction of UBXN2A targets metastatic characters of colon cancer cells. Our data indicates that VTD decreases the level of vascular endothelial growth factor (VEGF), a critical protein in the survival, invasion and migration of colon cancer cells. In in vivo studies, intraperitoneal injections of VTD over four weeks resulted in markedly increased levels of UBXN2A in colon tissues. In a UBXN2A dependent manner, VTD significantly suppressed progression of tumors formed in mouse model of CRC. Further characterization and modification of VTD will aid in the development of a druggable molecule to complement existing CRC therapies.

First Advisor

Khosrow Rezvani

Second Advisor

Jessica Freeling

Research Area

Basic Biomedical Sciences

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