Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A

Despite the worldwide research efforts to combat cancer, it remains a leading cause of death. Although various speci fi c kinase inhibitors already have been approved for clinical cancer treatment, occurrence of intrinsic or acquired resistance and intermittent response over longer periods limits long-term success of single kinase-targeted therapies. In this respect, there is a renewed interest in polypharmaceutical natural compounds, which simultaneously target various hyperactivated kinases involved in tumour-in fl ammation, angiogenesis, cell survival, proliferation, metastasis and angiogenesis. The dietary medicinal phytochemical withaferin A (WA), isolated from Withaferin somnifera (popular Indian name Ashwagandha), holds promise as a novel anti-cancer agent, which targets multiple cell survival kinase pathways, including I κ B kinase/NF- κ B, PI3 kinase/protein kinase B/mam- malian target of rapamycin and mitogen-activated protein kinase/extracellular signal- regulated kinase amongst others. In this review, we propose a novel mechanism of WA-dependent kinase inhibition via electrophilic covalent targeting of cysteine residues in conserved kinase activation domains (kinase cysteinome), which could underlie its pleio- tropic therapeutic effects in cancer signalling.

Jaar van publicatie:2017

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:6

CSS-citation score:1

Authors from:Higher Education

Toegankelijkheid:Open