1. PALP: A rapid imaging technique for stratifying ferroptosis sensitivity in normal and tumor tissues in situ.
- Author
-
Wang F, Graham ET, Naowarojna N, Shi Z, Wang Y, Xie G, Zhou L, Salmon W, Jia JM, Wang X, Huang Y, Schreiber SL, and Zou Y
- Subjects
- Animals, Cells, Cultured, Fatty Acids, Unsaturated analysis, Fluorescence, Lipid Peroxidation, Lipids chemistry, Male, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Multiphoton, Neoplasms, Experimental diagnostic imaging, Ferroptosis
- Abstract
Ferroptosis is an emerging cancer suppression strategy. However, how to select cancer patients for treating with ferroptosis inducers remains challenging. Here, we develop photochemical activation of membrane lipid peroxidation (PALP), which uses targeted lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation for reporting ferroptosis sensitivity in cells and tissues. PALP captured by BODIPY-C11 can be suppressed by lipophilic antioxidants and iron chelation, and is dependent on PUFA-lipid levels. Moreover, we develop PALPv2, for studying lipid peroxidation on selected membranes along the z axis in live cells using two-photon microscopes. Using PALPv1, we detect PUFA-lipids in multiple tissues, and validate a PUFA-phospholipid reduction during muscle aging as previously reported. Patterns of PALPv1 signals across multiple cancer cell types in vitro and in vivo are concordant with their ferroptosis susceptibility and PUFA-phospholipid levels. We envision that PALP will enable rapid stratification of ferroptosis sensitivity in cancer patients and facilitate PUFA-lipid research., Competing Interests: Declaration of interests S.L.S. serves on the Board of Directors of the Genomics Institute of the Novartis Research Foundation (“GNF”); is a shareholder and serves on the Board of Directors of Jnana Therapeutics; is a shareholder of Forma Therapeutics; is a shareholder and advises Kojin Therapeutics, Kisbee Therapeutics, Decibel Therapeutics, and Eikonizo Therapeutics; serves on the Scientific Advisory Boards of Eisai Co., Ltd., Ono Pharma Foundation, Exo Therapeutics, and F-Prime Capital Partners; and is a Novartis Faculty Scholar. Kojin Therapeutics, in particular, explores the medical potential of cell plasticity related to ferroptosis. Y.Z. is a consultant of Keen Therapeutics. The remaining authors declare no competing interests. A patent describing the utility of PALP in clinical samples was filed by Y.Z., F.W., Z.S., N.N., Y.W., G.X., and X.W., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF