Evaluating the role of sphingolipid signaling in paclitaxel-induced neurotoxicity of SH-SY5Y cells
Loading...
Date
2025-04
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Chemotherapies like paclitaxel and other similar microtubule targeting agents commonly used in breast cancer treatment can induce sensory peripheral neuropathy in patients, limiting dosage and impacting quality of life. One pathway implicated in chemotherapy induced peripheral neuropathy (CIPN) is sphingolipid signaling. To study the impact of microtubule targeting medications on sphingolipid signaling, SH-SY5Y cells were differentiated into neuron-like cells and treated with different concentrations of paclitaxel, both in the absence and presence of PF543, an inhibitor of sphingosine-kinase 1, the enzyme involved in the production of sphingosine-1-phosphate. Neurite degeneration was assessed using βIII-tubulin staining and high-content imaging. Imaging of paclitaxel-treated SH-SY5Y cells demonstrated neurotoxicity and a reduction in neuronal network complexity. However, PF543 did not exhibit neuroprotective effects under the tested conditions. Future studies may explore optimizing PF543 treatment parameters, such as preincubation, to assess potential protective effects. Additionally, liquid chromatography- mass spectrometry (LC-MS) is being employed to detect levels of ceramide, sphingosine, and sphingosine-1-phosphate. The impact of paclitaxel on sphingolipid signaling is being quantified to evaluate the involvement of this signaling pathway in neurotoxicity.
Description
Keywords
Chemotherapy Induced Peripheral Neuropathy, Sphingolipid Signaling, SH-SY5Y Cell Line, Paclitaxel, Liquid Chromatography-Mass Spectrometry