Fatty Acid Synthase as Interacting Anticancer Target of the Terpenoid Myrianthic Acid disclosed by MS-Based Proteomics Approaches

ABSTRACT: This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of Drug Affinity Responsive Target Stability (DARTS) and targeted-Limited Proteolysis coupled to Mass Spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural triteprenoid ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, in vitro biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the sig-nificance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start a potential development of innovative ap-proaches in therapy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Gilda D'Urso  

LAB HEAD: Agostino Casapullo

PROVIDER: PXD052306 | Pride | 2024-06-23

REPOSITORIES: Pride