The efficacy of ferroptosis-inducing compounds IKE and RSL3 correlates with the expression of ferroptotic pathway regulators CD71 and SLC7A11 in biliary tract cancer cells

• DOI: 10.1371/journal.pone.0302050
• Publication Date: 2024-04-11T20:16:10Z
• Authors: Dino Bekric; Tobias Kiesslich; Matthias Ocker; Martina Winklmayr; Markus Ritter; Heidemarie Dobias; Marlena Beyreis; Daniel Neureiter; Christian Mayr
• Keywords: Viability assay

Introduction Biliary tract cancer (BTC) is a lethal disease with bad overall survivability, partly arising from inadequate therapeutic alternatives, detection at belated stage, and resistance to common approaches. Ferroptosis form of programmed cell death that depends on reactive oxygen species (ROS) iron, causing excessive peroxidation polyunsaturated fatty acids (PUFAs). Therefore, the objective this investigation is, whether ferroptosis can be induced in BTC vitro induction dependent specific molecular markers. Methods The study conducted resazurin assay IC 25/50 calculation explore possible cytotoxic outcomes different classes ferroptosis-inducing substances (FINs) comprehensive model 11 lines. Combinatory treatments inhibitors were performed evaluate magnitude induction. To ascertain ferroptotic occurred, liperfluo iron kits employed lipid ROS intracellular abundance. Potential biomarkers sensitivity then assessed via western blot analysis, rtPCR panel functional kits. Results found FINs reduced viability line-dependent manner. In addition, we measured increased Fe 2+ levels upon exposure cells. Combining ferroptosis, necroptosis or apoptosis suggests occurrence events lines CCC-5, HuH-28 KKU-055. Furthermore, cells display heterogeneous profile regarding genes/markers ferroptosis. Subsequent analysis revealed towards IKE RSL3 positively correlated CD71 SLC7A11 protein expression. Conclusion Our results demonstrate promising approach inhibit growth might markers such as SLC7A11.