Abstract：
:Manassantin A is a natural product that has been shown to have anticancer activity in cell-based assays, but has a largely unknown mode-of-action. Described here is the use of two different energetics-based approaches to identify protein targets of manassantin A. Using the stability of proteins from rates of oxidation technique with an isobaric mass tagging strategy (iTRAQ-SPROX) and the pulse proteolysis technique with a stable isotope labeling with amino acids in cell culture strategy (SILAC-PP), over 1000 proteins in a MDA-MB-231 cell lysate grown under hypoxic conditions were assayed for manassantin A interactions (both direct and indirect). A total of 28 protein hits were identified with manassantin A-induced thermodynamic stability changes. Two of the protein hits (filamin A and elongation factor 1α) were identified using both experimental approaches. The remaining 26 hit proteins were only assayed in either the iTRAQ-SPROX or the SILAC-PP experiment. The 28 potential protein targets of manassantin A identified here provide new experimental avenues along which to explore the molecular basis of manassantin A's mode of action. The current work also represents the first application iTRAQ-SPROX and SILAC-PP to the large-scale analysis of protein-ligand binding interactions involving a potential anticancer drug with an unknown mode-of-action.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Geer Wallace MA,Kwon DY,Weitzel DH,Lee CT,Stephenson TN,Chi JT,Mook RA Jr,Dewhirst MW,Hong J,Fitzgerald MCdoi
10.1021/acs.jproteome.6b00237subject
Has Abstractpub_date
2016-08-05 00:00:00pages
2688-96issue
8eissn
1535-3893issn
1535-3907journal_volume
15pub_type
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