Determining the synergistic efficacy of tumor suppressant treatments on primary human renal cancer cell lines.
School Name
South Carolina Governor's School for Science and Mathematics
Grade Level
12th Grade
Presentation Topic
Cell and Molecular Biology
Presentation Type
Mentored
Abstract
Von Hippel-Lindau (VHL) syndrome, caused by the inactivation of the VHL tumor suppressor gene, is a disorder that induces the formation of tumors and cysts in patients, most commonly in the kidneys. Like all types of tumors, clear renal cell carcinomas require glutamate as the energy source. By acting as a glutaminase inhibitor to prevent the formation of glutamate from glutamine, CB-839 can effectively suppress tumor growth in a lab setting. This blockage increases the reactive oxygen species (ROS) in cancer cells, thus inducing stress that they are unable to tolerate. Despite the great efficacy of the drug during a short-term treatment, cancer cells can adjust their metabolic pathways to find new energy sources and reduce stress. LAT1 is a transport protein that functions in these new pathways, by removing excess glutamine, decreasing the efficacy of CB-839. JPH-203 inhibits the LAT1 transporter, preventing the cell from reducing the ROS. In vitro testing has shown both drugs to be effective as individual treatments. The purpose of the study was to confirm if the efficacy of CB-839 increases when cells are also exposed to JPH-203. We treated a primary human renal cancer cell line, UMRC3, with CB-839 and JPH-203 and monitored the cell growth through. a quantized crystal violet assay. We also evaluated the expression of proteins associated with glutamate metabolism by using western blot analysis. The combination of these drugs was shown to have greater efficacy as compared to either individually which indicates a possible tumor suppressant treatment for patients.
Recommended Citation
Kiaris, Charalampos, "Determining the synergistic efficacy of tumor suppressant treatments on primary human renal cancer cell lines." (2023). South Carolina Junior Academy of Science. 12.
https://scholarexchange.furman.edu/scjas/2023/all/12
Location
ECL 104
Start Date
3-25-2023 11:15 AM
Presentation Format
Oral Only
Group Project
No
Determining the synergistic efficacy of tumor suppressant treatments on primary human renal cancer cell lines.
ECL 104
Von Hippel-Lindau (VHL) syndrome, caused by the inactivation of the VHL tumor suppressor gene, is a disorder that induces the formation of tumors and cysts in patients, most commonly in the kidneys. Like all types of tumors, clear renal cell carcinomas require glutamate as the energy source. By acting as a glutaminase inhibitor to prevent the formation of glutamate from glutamine, CB-839 can effectively suppress tumor growth in a lab setting. This blockage increases the reactive oxygen species (ROS) in cancer cells, thus inducing stress that they are unable to tolerate. Despite the great efficacy of the drug during a short-term treatment, cancer cells can adjust their metabolic pathways to find new energy sources and reduce stress. LAT1 is a transport protein that functions in these new pathways, by removing excess glutamine, decreasing the efficacy of CB-839. JPH-203 inhibits the LAT1 transporter, preventing the cell from reducing the ROS. In vitro testing has shown both drugs to be effective as individual treatments. The purpose of the study was to confirm if the efficacy of CB-839 increases when cells are also exposed to JPH-203. We treated a primary human renal cancer cell line, UMRC3, with CB-839 and JPH-203 and monitored the cell growth through. a quantized crystal violet assay. We also evaluated the expression of proteins associated with glutamate metabolism by using western blot analysis. The combination of these drugs was shown to have greater efficacy as compared to either individually which indicates a possible tumor suppressant treatment for patients.
