2012
DOI: 10.1371/journal.pone.0039065
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Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior

Abstract: Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompa… Show more

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Cited by 91 publications
(94 citation statements)
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References 55 publications
(95 reference statements)
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“…Withaferin A (WIF-A), a steroidal lactone natural product derived from Withania somnifera, has been previously reported as a potent inhibitor of cancer growth (18,19) (SI Appendix, Fig. S5H).…”
Section: Anti-biotinmentioning
confidence: 99%
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“…Withaferin A (WIF-A), a steroidal lactone natural product derived from Withania somnifera, has been previously reported as a potent inhibitor of cancer growth (18,19) (SI Appendix, Fig. S5H).…”
Section: Anti-biotinmentioning
confidence: 99%
“…WIF-A is thought to induce cell death of VIM-expressing cancer cells, at least in part, by inducing filamentous network collapse and degradation of VIM (18,19). To monitor the assembly status of the VIM filamentous architecture, we performed immunofluorescent analyses of FiVe1-and WIF-A-treated human umbilical endothelial cells (HUVECs), which have been shown to display a high elaborated VIM architecture sensitive to WIF-A treatment (20).…”
Section: Anti-biotinmentioning
confidence: 99%
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“…Affinity purification studies have shown that WFA binds to vimentin as well as other intermediate filament proteins including glial fibrillary acidic protein and desmin [60,61]. WFA also downregulates the expression of these filament proteins as well as peripherin [62] resulting in substantial cytoskeletal perturbation in affected cells [60][61][62][63] suggesting that WFA is a potent inhibitor of type III intermediate filaments as well. One study reported that WFA binds covalently to cysteine 328 of vimentin [60], although another study suggested that the effects of WFA on vimentin disruption are not dependent cysteine 328 binding [62].…”
Section: Cytoskeletal Organizing and Structural Proteinsmentioning
confidence: 99%
“…WFA also downregulates the expression of these filament proteins as well as peripherin [62] resulting in substantial cytoskeletal perturbation in affected cells [60][61][62][63] suggesting that WFA is a potent inhibitor of type III intermediate filaments as well. One study reported that WFA binds covalently to cysteine 328 of vimentin [60], although another study suggested that the effects of WFA on vimentin disruption are not dependent cysteine 328 binding [62]. Subsequent studies suggested that WFA might alter vimentin distribution through affecting its phosphorylation [64,65].…”
Section: Cytoskeletal Organizing and Structural Proteinsmentioning
confidence: 99%