Evaluating Potential TASK-1 Inhibitors for Anti-cancer Therapies
Gianna Kiszka
Co-Presenters: Sofiia Korotka
College: The Dorothy and George Hennings College of Science, Mathematics and Technology
Major: Biotechnology/Molecular Biology - STEM 5 Year B.S./M.S.
Faculty Research Mentor: Thomas Comollo
Abstract:
TASK-1 (TWIK-related acid-sensitive potassium channel 1), encoded by the KCNK3 gene, regulates cell excitability and has been implicated in the survival of non-small cell lung cancer cells by bypassing apoptosis. This study aims to identify small molecules that can inhibit TASK-1 channels, using in silico docking simulations followed by in vitro validation. Previously, virtual screening of approximately 1,000,000 small molecules from the ZINC12 database led to identifying KU124 as a promising candidate. KU124 was tested using CHO cells expressing inducible TASK-1-GFP, and TASK-1 channel activity was measured via thallium flux assay. Results showed that KU124 inhibited TASK-1 channel conductance in vitro, however, its anticancer properties or lack thereof remained inconclusive. In the current phase of this research, we continue to test KU124 on a freshly started lung cancer cell line and glioma (U87) cells to verify our previous results. Additionally, we are testing niclosamide, doxapram, and cisplatin to evaluate their potential as anti-cancer agents. These studies could lead to the development of novel therapeutic strategies for targeting TASK-1 in cancer treatment.Keywords: TASK-1, non-small cell lung cancer (NSCLC), inhibitors, anti-cancer agents