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
2011-11-30
发表期刊EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN0014-2999
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
资助信息National Natural Science Foundation of China[90813028, 30801387, 30930101, 81072220]; Ministry of Science and Technology[2009CB522300, 2011CB504300]
学科领域Pharmacology & Pharmacy
DOI10.1016/j.ejphar.2011.08.026
收录类别SCI
语种英语
WOS研究方向Pharmacology & Pharmacy
WOS类目Pharmacology & Pharmacy
WOS记录号WOS:000297449000012
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
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
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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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