Therapy-induced senescence is a state of cell cycle arrest that occurs as a response to stress. Chemotherapeutics can cause senescence through DNA damage and, through their secretory phenotype, senescent cells greatly hinder the effectiveness of chemotherapy and can contribute to cancer reoccurrence. Senescent cells are resistant to cell death and are characterized through widespread changes to their gene expression. However, less is known about the characterization of changes to the lipidome of senescent cells. Lipids play important roles in other cellular processes and could provide a better understanding of senescence. The goal of this work is to characterize lipid changes in senescent cells and ultimately provide a means to improve the efficacy of chemotherapy. To achieve this goal, a tissue culture model system was established, and lipid changes were analyzed to identify key lipids involved in therapy-induced senescence. Senescence was induced using doxorubicin and mass spectrometry-based profiling was utilized to study lipid changes. Using an untargeted approach, the global lipid composition of proliferating and senescent cells was compared, which revealed significant changes in sphingolipids. Further investigations revealed that modulating the levels of different sphingolipids could rescue cells from senescence. This work indicates that sphingolipid levels and localization may play an important role in senescence and suggests a novel role for certain sphingolipids in therapy-induced senescence.

Involvement of sphingolipids in therapy-induced senescence

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.