Profiling Intact Glycosphingolipids with Automated Structural Annotation and Quantitation from Human Samples with Nanoflow Liquid Chromatography Mass Spectrometry.

Sphingolipids are an essential subset of bioactive lipids found in most eukaryotic cells that contribute to membrane biophysical properties and are involved in cellular differentiation, recognition, and mediating interactions. The described nanoHPLC-ESI-Q/ToF methodology utilizes known biosynthetic pathways, accurate mass detection, optimized collision-induced disassociation, and a robust nanoflow chromatographic separation for the analysis of intact sphingolipids found in human tissue, cells, and serum. The methodology was developed and validated with an emphasis on addressing the common issues experienced in profiling these amphipathic lipids, which are part of the glycocalyx and lipidome.

Integrating Computational Methods in Network Pharmacology and Screening to Uncover Multi-targeting Phytochemicals against Aberrant Protein Glycosylation in Lung Cancer.

Glycoproteins are an underexploited drug target for cancer therapeutics. In this work, we integrated computational methods in network pharmacology and docking approaches to identify phytochemical compounds that could potentially interact with several cancer-associated glycoproteins. We first created a database of phytochemicals from selected plant species, (sapodilla/chico), (mango), (soursop/guyabano), (jackfruit/langka), (langsat/lanzones), and (bignay), and performed pharmacokinetic analysis to determine their drug-likeness properties.

Comparative proteomics reveals anticancer compounds from Lansium domesticum against NSCLC cells target mitochondrial processes.

Lansium domesticum is identified as a potential source of anticancer compounds. However, there are minimal studies on its anti-lung cancer properties as well as its mechanism of action. Here, we show the specificity of lanzones hexane (LH) leaf extracts to non-small cell lung cancer cells (A549) compared to normal lung fibroblast cells (CCD19-Lu) and normal epithelial prostate cells (PNT2).

Biological Assay-Guided Fractionation and Mass Spectrometry-Based Metabolite Profiling of L. Cytotoxic Compounds against Lung Cancer A549 Cell Line.

L. (Guyabano) leaves are reported to exhibit anticancer activity against cancer cells. In this study, the ethyl acetate extract from guyabano leaves was purified through column chromatography, and the cytotoxic effects of the semi-purified fractions were evaluated against A549 lung cancer cells using in vitro MTS cytotoxicity and scratch/wound healing assays.

An Integrated Mass Spectrometry-Based Glycomics-Driven Glycoproteomics Analytical Platform to Functionally Characterize Glycosylation Inhibitors.

Cancer progression is linked to aberrant protein glycosylation due to the overexpression of several glycosylation enzymes. These enzymes are underexploited as potential anticancer drug targets and the development of rapid-screening methods and identification of glycosylation inhibitors are highly sought. An integrated bioinformatics and mass spectrometry-based glycomics-driven glycoproteomics analysis pipeline was performed to identify an N-glycan inhibitor against lung cancer cells.

screening-based discovery of inhibitors against glycosylation proteins dysregulated in cancer.

Targeting enzymes associated with the biosynthesis of aberrant glycans is an under-utilized strategy in discovering potential inhibitors or drugs against cancer. The formation of cancer-associated glycans is mainly due to the dysregulated expression of glycosyltransferases and glycosidases, which play crucial roles in maintaining cellular structure and function. We screened a database of more than 14,000 compounds consisting of natural products and drugs for inhibition against four glycosylation enzymes - Alpha1-6FucT, ST6Gal1, ERMan1, and GlcNAcT-V.