FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2039345087> ?p ?o ?g. }

• W2039345087 endingPage "1865" @default.
• W2039345087 startingPage "1852" @default.
• W2039345087 abstract "Withaferin A (WA), a C5,C6-epoxy steroidal lactone derived from a medicinal plant (Withania somnifera), inhibits growth of human breast cancer cells in vitro and in vivo and prevents mammary cancer development in a transgenic mouse model. However, the mechanisms underlying the anticancer effect of WA are not fully understood. Herein, we report that tubulin is a novel target of WA-mediated growth arrest in human breast cancer cells. The G2 and mitotic arrest resulting from WA exposure in MCF-7, SUM159, and SK-BR-3 cells was associated with a marked decrease in protein levels of β-tubulin. These effects were not observed with the naturally occurring C6,C7-epoxy analogs of WA (withanone and withanolide A). A non-tumorigenic normal mammary epithelial cell line (MCF-10A) was markedly more resistant to mitotic arrest by WA compared with breast cancer cells. Vehicle-treated control cells exhibited a normal bipolar spindle with chromosomes aligned along the metaphase plate. In contrast, WA treatment led to a severe disruption of normal spindle morphology. NMR analyses revealed that the A-ring enone in WA, but not in withanone or withanolide A, was highly reactive with cysteamine and rapidly succumbed to irreversible nucleophilic addition. Mass spectrometry demonstrated direct covalent binding of WA to Cys(303) of β-tubulin in MCF-7 cells. Molecular docking indicated that the WA-binding pocket is located on the surface of β-tubulin and characterized by a hydrophobic floor, a hydrophobic wall, and a charge-balanced hydrophilic entrance. These results provide novel insights into the mechanism of growth arrest by WA in breast cancer cells." @default.
• W2039345087 created "2016-06-24" @default.
• W2039345087 creator A5018024103 @default.
• W2039345087 creator A5020551704 @default.
• W2039345087 creator A5022304953 @default.
• W2039345087 creator A5037710598 @default.
• W2039345087 creator A5038966523 @default.
• W2039345087 creator A5042534461 @default.
• W2039345087 creator A5047780776 @default.
• W2039345087 creator A5052471392 @default.
• W2039345087 creator A5054945469 @default.
• W2039345087 creator A5055116819 @default.
• W2039345087 creator A5064924657 @default.
• W2039345087 creator A5069231811 @default.
• W2039345087 creator A5074170620 @default.
• W2039345087 creator A5078706989 @default.
• W2039345087 creator A5087198268 @default.
• W2039345087 date "2014-01-01" @default.
• W2039345087 modified "2023-10-13" @default.
• W2039345087 title "Growth Arrest by the Antitumor Steroidal Lactone Withaferin A in Human Breast Cancer Cells Is Associated with Down-regulation and Covalent Binding at Cysteine 303 of β-Tubulin" @default.
• W2039345087 cites W1527645849 @default.
• W2039345087 cites W1963895146 @default.
• W2039345087 cites W1964324812 @default.
• W2039345087 cites W1964483457 @default.
• W2039345087 cites W1971579914 @default.
• W2039345087 cites W1982978735 @default.
• W2039345087 cites W1991366673 @default.
• W2039345087 cites W1992362205 @default.
• W2039345087 cites W1993646281 @default.
• W2039345087 cites W1995405908 @default.
• W2039345087 cites W1996331246 @default.
• W2039345087 cites W2006242390 @default.
• W2039345087 cites W2010993054 @default.
• W2039345087 cites W2017758465 @default.
• W2039345087 cites W2031554805 @default.
• W2039345087 cites W2040556616 @default.
• W2039345087 cites W2048109276 @default.
• W2039345087 cites W2048454522 @default.
• W2039345087 cites W2051652522 @default.
• W2039345087 cites W2060259273 @default.
• W2039345087 cites W2066179074 @default.
• W2039345087 cites W2072986748 @default.
• W2039345087 cites W2075177133 @default.
• W2039345087 cites W2075277027 @default.
• W2039345087 cites W2077173514 @default.
• W2039345087 cites W2082552678 @default.
• W2039345087 cites W2086526874 @default.
• W2039345087 cites W2093234844 @default.
• W2039345087 cites W2095826096 @default.
• W2039345087 cites W2099439152 @default.
• W2039345087 cites W2099623371 @default.
• W2039345087 cites W2102845038 @default.
• W2039345087 cites W2103518432 @default.
• W2039345087 cites W2105668062 @default.
• W2039345087 cites W2105805458 @default.
• W2039345087 cites W2107277218 @default.
• W2039345087 cites W2111669022 @default.
• W2039345087 cites W2122870721 @default.
• W2039345087 cites W2125516679 @default.
• W2039345087 cites W2132105604 @default.
• W2039345087 cites W2134842491 @default.
• W2039345087 cites W2137388847 @default.
• W2039345087 cites W2137736893 @default.
• W2039345087 cites W2141647078 @default.
• W2039345087 cites W2153977062 @default.
• W2039345087 cites W2157011569 @default.
• W2039345087 doi "https://doi.org/10.1074/jbc.m113.496844" @default.
• W2039345087 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3894360" @default.
• W2039345087 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24297176" @default.
• W2039345087 hasPublicationYear "2014" @default.
• W2039345087 type Work @default.
• W2039345087 sameAs 2039345087 @default.
• W2039345087 citedByCount "103" @default.
• W2039345087 countsByYear W20393450872014 @default.
• W2039345087 countsByYear W20393450872015 @default.
• W2039345087 countsByYear W20393450872016 @default.
• W2039345087 countsByYear W20393450872017 @default.
• W2039345087 countsByYear W20393450872018 @default.
• W2039345087 countsByYear W20393450872019 @default.
• W2039345087 countsByYear W20393450872020 @default.
• W2039345087 countsByYear W20393450872021 @default.
• W2039345087 countsByYear W20393450872022 @default.
• W2039345087 countsByYear W20393450872023 @default.
• W2039345087 crossrefType "journal-article" @default.
• W2039345087 hasAuthorship W2039345087A5018024103 @default.
• W2039345087 hasAuthorship W2039345087A5020551704 @default.
• W2039345087 hasAuthorship W2039345087A5022304953 @default.
• W2039345087 hasAuthorship W2039345087A5037710598 @default.
• W2039345087 hasAuthorship W2039345087A5038966523 @default.
• W2039345087 hasAuthorship W2039345087A5042534461 @default.
• W2039345087 hasAuthorship W2039345087A5047780776 @default.
• W2039345087 hasAuthorship W2039345087A5052471392 @default.
• W2039345087 hasAuthorship W2039345087A5054945469 @default.
• W2039345087 hasAuthorship W2039345087A5055116819 @default.
• W2039345087 hasAuthorship W2039345087A5064924657 @default.
• W2039345087 hasAuthorship W2039345087A5069231811 @default.
• W2039345087 hasAuthorship W2039345087A5074170620 @default.
• W2039345087 hasAuthorship W2039345087A5078706989 @default.

• next