HS-173 as a novel inducer of RIP3-dependent necroptosis in lung cancer

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dc.contributor.authorJung Hee Park-
dc.contributor.authorKyung Hee Jung-
dc.contributor.authorSoo Jung Kim-
dc.contributor.authorYoung-Chan Yoon-
dc.contributor.authorHong Hua Yan-
dc.contributor.authorZhenghuan Fang-
dc.contributor.authorJi Eun Lee-
dc.contributor.authorJoo Han Lim-
dc.contributor.authorShinmee Mah-
dc.contributor.authorSungwoo Hong-
dc.contributor.authorYou-Sun Kim-
dc.contributor.authorSoon-Sun Hong-
dc.date.available2019-02-20T08:15:50Z-
dc.date.created2019-01-28-
dc.date.issued2019-03-
dc.identifier.issn0304-3835-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/5596-
dc.description.abstractNecroptosis is a form of regulated necrotic cell death mediated by receptor-interacting kinase 3 (RIP3). Recently, necroptosis has gained attention as a novel alternative therapy to target cancer cells. In this study, we screened several chemotherapeutics used in preclinical and clinical studies, and identified a drug HS-173 that induces RIP3-mediated necroptosis. HS-173 decreased the cell survival in a dose-dependent manner in RIP3-expressing lung cancer cells, compared to the cells lacking RIP3. Also, the cell death induced by HS-173 was rescued by specific necroptosis inhibitors such as necrostatin-1 and dabrafenib. Additionally, HS-173 increased the phosphorylation of RIP3 and MLKL, which was decreased by necroptosis inhibitors, indicating that HS-173 activates RIP3/MLKL signaling in lung cancer cells. HS-173 increased the necroptotic events, as observed by the increased levels of HMGB1 and necroptotic morphological features. Furthermore, HS-173 inhibited the tumor growth by stimulation of necroptosis in mouse xenograft models. Our findings offer new insights into the role of HS-173 in inducing necroptosis by enhancing RIP3 expression and activating the RIP3/MLKL signaling pathway in lung cancer cells. © 2018 Elsevier B.V-
dc.languageENG-
dc.publisherELSEVIER IRELAND LTD-
dc.titleHS-173 as a novel inducer of RIP3-dependent necroptosis in lung cancer-
dc.typeArticle-
dc.type.rimsA-
dc.identifier.wosid000457505400009-
dc.identifier.scopusid2-s2.0-85059150046-
dc.contributor.affiliatedAuthorShinmee Mah-
dc.contributor.affiliatedAuthorSungwoo Hong-
dc.identifier.bibliographicCitationCANCER LETTERS, v.444, no., pp.94 - 104-
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Center for Catalytic Hydrocarbon Functionalizations(분자활성 촉매반응 연구단) > Journal Papers (저널논문)
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