坏死性下垂
诱导剂
程序性细胞死亡
肺癌
癌细胞
癌症
激酶
癌症研究
医学
信号转导
细胞生物学
细胞凋亡
化学
生物
生物化学
遗传学
作者
Jung Hee Park,Kyung Hee Jung,Soo Jung Kim,Young-Chan Yoon,Pengcheng Zhang,Zhenghuan Fang,Ji Eun Lee,Joo Han Lim,Shinmee Mah,Sungwoo Hong,You‐Sun Kim,Soon‐Sun Hong
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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