LAT1 Drug Conjugates as Selective Cancer Therapeutics
Faculty Mentor
Dr. Jannet Kocerha
Location
Russell Union Room 2054
Type of Research
On-going
Session Format
Oral Presentation
College
Jack Averitt College of Graduate Studies
Department
Chemistry, Biochemistry, & Physics
Abstract
Cancer cells exhibit abnormal metabolic properties to supply the cell with the necessary nutrients to proliferate at an increased rate. One of these abnormalities is the increased activity of the L-type Amino Acid Transporter 1, LAT1. The synthesis of drug conjugates that link structures with known cytotoxicity, 1,4-naphthoquinone and 9-aminoacridine, to LAT1-recognized substrates allows selective cytotoxicity toward cancerous over non-cancerous cells. Our group designed, synthesized, and characterized several of these drug conjugates with several cancer cell lines, all of which are a part of the NCI60 panel, as well as with cells of a non-cancerous origin (HEK293T cells). Cell viability at a few timepoints and IC50 values were quantitated with a colorimetric based MTS assay. Changes in nuclei number and morphology were visualized with Confocal microscopy, along with intracellular localization of the inherently fluorescent acridine-LAT1 conjugates. All LAT1 targeting compounds showed potent cytotoxic selectivity towards cancerous cell lines compared to HEK293. Future studies will evaluate intracellular targets of the compounds as well as further investigate the LAT-1 mediated selectivity with competition assays and silencing of LAT1.
Program Description
.
Start Date
4-23-2026 10:00 AM
End Date
4-23-2026 10:15 AM
Recommended Citation
Williams, Dylan J., "LAT1 Drug Conjugates as Selective Cancer Therapeutics" (2026). GS4 Student Scholars Symposium. 11.
https://digitalcommons.georgiasouthern.edu/research_symposium/2026/2026/11
LAT1 Drug Conjugates as Selective Cancer Therapeutics
Russell Union Room 2054
Cancer cells exhibit abnormal metabolic properties to supply the cell with the necessary nutrients to proliferate at an increased rate. One of these abnormalities is the increased activity of the L-type Amino Acid Transporter 1, LAT1. The synthesis of drug conjugates that link structures with known cytotoxicity, 1,4-naphthoquinone and 9-aminoacridine, to LAT1-recognized substrates allows selective cytotoxicity toward cancerous over non-cancerous cells. Our group designed, synthesized, and characterized several of these drug conjugates with several cancer cell lines, all of which are a part of the NCI60 panel, as well as with cells of a non-cancerous origin (HEK293T cells). Cell viability at a few timepoints and IC50 values were quantitated with a colorimetric based MTS assay. Changes in nuclei number and morphology were visualized with Confocal microscopy, along with intracellular localization of the inherently fluorescent acridine-LAT1 conjugates. All LAT1 targeting compounds showed potent cytotoxic selectivity towards cancerous cell lines compared to HEK293. Future studies will evaluate intracellular targets of the compounds as well as further investigate the LAT-1 mediated selectivity with competition assays and silencing of LAT1.
