DAPK1 mediates the G1 phase arrest in human nasopharyngeal carcinoma cells induced by grifolin, a potential antitumor natural product | |
Luo, Xiang-jian2; Li, Wei2; Yang, Li-fang2; Yu, Xin-fang2; Xiao, Lan-bo2; Tang, Min2; Dong, Xin2; Deng, Qi-pan2; Bode, Ann M.3; Liu, Ji-kai1; Cao, Ya2 | |
通讯作者 | Liu, JK (reprint author), Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resource W China, Kunming 650204, Yunnan, Peoples R China |
2011-11-30 | |
发表期刊 | EUROPEAN JOURNAL OF PHARMACOLOGY |
ISSN | 0014-2999 |
卷号 | 670期号:2-3页码:427-434 |
摘要 | Grifolin, a secondary metabolite isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, has been shown to induce Cl phase cell-cycle arrest in tumor cells in previous studies of our group. However, the mechanisms of action are not completely understood. Our group further demonstrated that grifolin upregulates death-associated protein kinase 1 (DAPK1) in nasopharyngeal carcinoma cells (NPCs). Here, we found that grifolin induced dephosphorylation of DAPK1 (Ser308) to activate DAPK1 and subsequent phosphorylation of its potential downstream effector p21 (Thr145) in nasopharyngeal carcinoma cell CNE1. Inhibition of DAPK1 by introducing siRNA targeting DAPK1 reversed the grifolin- induced phosphorylation of p21. Furthermore, we confirmed that grifolin increased the half-life of p21 and promoted its stability. Flow cytometry analysis demonstrated that DAPK1 was involved in grifolin-induced Cl phase arrest in CNE1 cells. The similar effects induced by grifolin and mechanism beneath were identified in another nasopharyngeal carcinoma cell HONE1. In addition, we observed that grifolin promoted the protein-protein interaction of DAPK1 and ERK1/2 to prevent ERK1/2 nucleolus translocation. Our findings indicate that DAPK1 plays a crucial role in the induction of cell-cycle arrest at Cl phase by grifolin. Grifolin might represent a promising candidate in the prevention and intervention of cancer by targeting DAPK1 signaling to induce cell cycle Cl phase arrest. (C) 2011 Elsevier B.V. All rights reserved. |
关键词 | Grifolin Dapk1 Cell Cycle P21 Erk1/2 Npc Mushroom |
学科领域 | Pharmacology & Pharmacy |
DOI | 10.1016/j.ejphar.2011.08.026 |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000297449000012 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.kib.ac.cn/handle/151853/5325 |
专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
作者单位 | 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resource W China, Kunming 650204, Yunnan, Peoples R China 2.Cent S Univ, Xiangya Sch Med, Canc Res Inst, Changsha 410078, Hunan, Peoples R China 3.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA |
推荐引用方式 GB/T 7714 | Luo, Xiang-jian,Li, Wei,Yang, Li-fang,et al. DAPK1 mediates the G1 phase arrest in human nasopharyngeal carcinoma cells induced by grifolin, a potential antitumor natural product[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2011,670(2-3):427-434. |
APA | Luo, Xiang-jian.,Li, Wei.,Yang, Li-fang.,Yu, Xin-fang.,Xiao, Lan-bo.,...&Cao, Ya.(2011).DAPK1 mediates the G1 phase arrest in human nasopharyngeal carcinoma cells induced by grifolin, a potential antitumor natural product.EUROPEAN JOURNAL OF PHARMACOLOGY,670(2-3),427-434. |
MLA | Luo, Xiang-jian,et al."DAPK1 mediates the G1 phase arrest in human nasopharyngeal carcinoma cells induced by grifolin, a potential antitumor natural product".EUROPEAN JOURNAL OF PHARMACOLOGY 670.2-3(2011):427-434. |
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