坏死性下垂
程序性细胞死亡
癌细胞
癌症
激酶
癌症研究
信号转导
细胞生物学
细胞凋亡
生物
生物化学
遗传学
作者
Jung Hee Park,Kyung Hee Jung,Soo Jung Kim,Young‐Chan Yoon,Hong Yan,Zhenghuan Fang,Ji Eun Lee,Joo Han Lim,Shinmee Mah,Sungwoo Hong,You‐Sun Kim,Soon‐Sun Hong
出处
期刊:Cancer Letters
[Elsevier BV]
日期:2018-12-22
卷期号:444: 94-104
被引量:21
标识
DOI:10.1016/j.canlet.2018.12.006
摘要
Necroptosis 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.
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