Xanthohumol induces paraptosis of leukemia cells through p38 mitogen activated protein kinase signaling pathway

作者：Xiangquan Mi, Chunming Wang, Chao Sun, Xu Chen, Xiang Huo, Yiming Zhang, Gang Li, Bo Xu, Jun Zhang, Jianxin Xie, Zhenhua Wang, Ji Li · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.16185 · 被引用次数：46 · 研究领域：Hops Chemistry and Applications、Toxin Mechanisms and Immunotoxins、PI3K/AKT/mTOR signaling in cancer

// Xiangquan Mi 1, 2 , Chunming Wang 1 , Chao Sun 3 , Xu Chen 1 , Xiang Huo 1 , Yiming Zhang 2 , Gang Li 2 , Bo Xu 2 , Jun Zhang 4 , Jianxin Xie 4 , Zhenhua Wang 2 , Ji Li 2 1 School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China 2 Center for Mitochondrial and Healthy Aging, College of Life Sciences, Yantai University, Yantai, Shandong 264005, P.R. China 3 Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, P.R. China 4 Shihezi University School of Medicine, Shihezi, Xinjiang 832000, P.R. China Correspondence to: Ji Li, email: lijimelissafang@yahoo.com Keywords: xanthohumol, paraptosis, p38-MAPK, cytoplasmic vacuolation, ER stress Received: November 22, 2016      Accepted: March 06, 2017      Published: March 14, 2017 ABSTRACT Xanthohumol as a natural polyphenol demonstrates an anticancer activity, but its underlying mechanism remains unclear. In this study, we showed that xanthohumol (XN) induces paraptosis of leukemia cells. The paraptosis is one cell death which is characterized by dilation of the endoplasmic reticulum and/or mitochondria. The results demonstrated that XN treatment significantly inhibited cell proliferation and triggered extensive cytoplasmic vacuolation of HL-60 leukemia cells, but it did not cause the cleavage of caspase-3 protein or apoptosis. In contrast, XN treatment resulted in LC3-II accumulation through blocking of autophagosome maturation. Interestingl...