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- W2110404738 abstract "Withaferin A (WFA) is a steroidal lactone with antitumor effects manifested at multiple levels that are mechanistically obscure. Using a phospho-kinase screening array, we discovered that WFA activated phosphorylation of the S6 kinase RSK (ribosomal S6 kinase) in breast cancer cells. Pursuing this observation, we defined activation of extracellular signal-regulated kinase (ERK)-RSK and ETS-like transcription factor 1 (Elk1)-CHOP (C-EBP homologous protein) kinase pathways in upregulating transcription of the death receptor 5 (DR5). Through this route, WFA acted as an effective DR5 activator capable of potentiating the biologic effects of celecoxib, etoposide, and TRAIL. Accordingly, WFA treatment inhibited breast tumor formation in xenograft and mouse mammary tumor virus (MMTV)-neu mouse models in a manner associated with activation of the ERK/RSK axis, DR5 upregulation, and elevated nuclear accumulation of Elk1 and CHOP. Together, our results offer mechanistic insight into how WFA inhibits breast tumor growth." @default.
- W2110404738 created "2016-06-24" @default.
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- W2110404738 date "2014-04-30" @default.
- W2110404738 modified "2023-10-13" @default.
- W2110404738 title "Mechanistic Elucidation of the Antitumor Properties of Withaferin A in Breast Cancer" @default.
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- W2110404738 doi "https://doi.org/10.1158/0008-5472.can-13-2081" @default.
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- W2110404738 hasPublicationYear "2014" @default.
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