Proteomic characterization of Withaferin A-targeted protein networks for the treatment of monoclonal myeloma gammopathies

ABSTRACT: Withaferin A (WA), a natural steroid lactone from the plant Withania Somnifera, has been used for many years in traditional Ayurveda medicine to treat inflammation-related conditions, such as ulcers and rheumatism. Today, WA is most often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and of its mechanism of antitumor action remains incomplete. Here, we used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis (IPA) and Western Blot. Canonical pathway analysis revealed targeting of the ubiquitination pathway as a main strategy for WA-induced cell death. Further data suggested that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM). Moreover, 16 of 20 proteins influenced by WA potentially counteract disease progression, suggesting WA can be used as an effective treatment for MGUS and other closely related disorders.

INSTRUMENT(S): LTQ Orbitrap Velos, 4800 Proteomics Analyzer

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Culture

SUBMITTER: martin dom  

LAB HEAD: Xaveer Van Ostade

PROVIDER: PXD006528 | Pride | 2018-02-23

REPOSITORIES: Pride