UROP Fellowship: Engineering
Research Mentor(s): Korie Grayson, PhD
Research Mentor Institution/Department: College of Engineering, Department of Chemical Engineering
Presentation Date: Wednesday, August 4th
Session: Session 2 (4pm-4:50pm EDT)
Breakout Room: Room 1
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Current treatments for colorectal cancer include surgery, radiation, and chemotherapy; however, the five-year survival rate for distant CRC is 16%. Due to the ineffectiveness of standard treatments, especially at distant CRC, new therapeutics are needed to provide more effective treatment options at all stages. Bile acids produced in the liver and secreted into the small intestine are responsible for breaking down and absorbing ingested lipids. These endogenous bile acids have been shown to induce apoptosis in CRC cells. Deoxycholic acid (DCA) is a secondary bile acid that has been shown to induce apoptosis at high concentrations, 500 µM or above; however, DCA promotes the proliferation of CRC cells at lower concentrations. Another secondary bile salt, ursodeoxycholic acid (UDCA), can reduce the proliferation of colorectal cancer cells while protecting surrounding healthy tissue.
CRC cell lines, HT-29 and Caco-2, were treated with DCA and UDCA at 50µM, 125µM, 250µM, and 500µM to determine their effects on cell viability. Cells were harvested using Accutase and analyzed with AnnexinV/PI flow cytometry assay. Viable cells were labeled as AV-/PI-, early apoptotic cells as AV+/PI-, late-stage apoptotic cells as AV+/PI+, and necrotic cells as AV-/PI+. At 500 uM, DCA significantly reduced cell viability in both HT-29 and Caco-2 cell lines, by 75% and 20% respectively. UDCA did not effectively induce apoptosis in HT-29 cells with cell viability remaining >90% in each treatment group. This may suggest that at this concentration UDCA provides protection of the cells, which can be utilized in cancer treatments to preserve noncancerous cells. However, for Caco-2, there was a decrease in cell viability with UDCA for every tested concentration.
Based on these results, DCA can be utilized as a treatment for colorectal cancer to induce apoptosis in CRC cell lines at high concentrations. However, DCA decreased cell viability significantly more in Caco-2 cells, which suggests effectiveness in inducing apoptosis may vary across different CRC cell lines. Further exploration of cancer drug resistance mechanisms for each cell line can lead to a better understanding of individualized patient responses to different drug treatments. DCA could be used to target cancer cells specifically using nanoparticle delivery systems, which would allow for DCA to affect only cancerous cells. The observed behavior of UDCA suggests it may be used to preserve healthy cells using a similar delivery system. The simultaneous delivery of DCA and UDCA within certain concentration ranges could reduce the proliferation of cancer cells, protect surrounding healthy cells, while selectively inducing apoptosis in CRC cells.