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Molecular Signal Processing
Bioorganic Chemistry
Biochemistry of Plant Interactions
Cell and Metabolic Biology
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Publications - Cell and Metabolic Biology
Publications
A bottleneck in the development of new anti‐cancer drugs is the recognition of their mode of action (MoA). Metabolomics combined with machine learning allowed to predict MoAs of novel anti‐proliferative drug candidates, focusing on human prostate cancer cells (PC‐3). As proof of concept, 38 drugs are studied with known effects on 16 key processes of cancer metabolism, profiling low molecular weight intermediates of the central carbon and cellular energy metabolism (CCEM) by LC‐MS/MS. These metabolic patterns unveiled distinct MoAs, enabling accurate MoA predictions for novel agents by machine learning. The transferability of MoA predictions based on PC‐3 cell treatments is validated with two other cancer cell models, i.e., breast cancer and Ewing\'s sarcoma, and show that correct MoA predictions for alternative cancer cells are possible, but still at some expense of prediction quality. Furthermore, metabolic profiles of treated cells yield insights into intracellular processes, exemplified for drugs inducing different types of mitochondrial dysfunction. Specifically, it is predicted that pentacyclic triterpenes inhibit oxidative phosphorylation and affect phospholipid biosynthesis, as confirmed by respiration parameters, lipidomics, and molecular docking. Using biochemical insights from individual drug treatments, this approach offers new opportunities, including the optimization of combinatorial drug applications.
Publications
In contrast to animal lectins, no evidence has indicated the occurrence of plant lectins, which recognize and bind “endogenous” receptors and accordingly are involved in recognition mechanisms within the organism itself. Here we show that the plant hormone jasmonic acid methyl ester (JAME) induces in leaves of Nicotiana tabacum (var. Samsun NN) the expression of a lectin that is absent from untreated plants. The lectin specifically binds to oligomers of N‐acetylglucosamine and is detected exclusively in the cytoplasm and the nucleus. Both the subcellular location and specificity indicate that the Nicotiana tabacum agglutinin (called Nictaba) may be involved in the regulation of gene expression in stressed plants through specific protein‐carbohydrate interactions with regulatory cytoplasmic/nuclear glycoproteins. Searches in the databases revealed that many flowering plants contain sequences encoding putative homologues of the tobacco lectin, which suggest that Nictaba is the prototype of a widespread or possibly ubiquitous family of lectins with a specific endogenous role.
This page was last modified on 27 Jan 2025 .
