Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells
Luo, Xiang-jian1; Li, Li-li1; Deng, Qi-pan1; Yu, Xin-fang1; Yang, Li-fang1; Luo, Fei-jun1; Xiao, Lan-bo1; Chen, Xiao-yan1; Ye, Mao1; Liu, Ji-kai2; Cao, Ya1
2011
发表期刊EUROPEAN JOURNAL OF CANCER
ISSN0959-8049
卷号47期号:2页码:316-325
摘要Grifolin, a secondary metabolite isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, has been shown to inhibit the growth of some cancer cell lines in vitro by induction of apoptosis in previous studies of our group. However, the mechanisms of action are not completely understood. An apoptosis-related gene expression profiling analysis provided a clue that death-associated protein kinase 1 (dapk1) gene was upregulated at least twofold in response to grifolin treatment in nasopharyngeal carcinoma cell CNE1. Here, we further investigated the role of DAPK1 in apoptotic effect induced by grifolin. We observed that protein as well as mRNA level of DAPK1 was induced by grifolin in a dose-dependent manner in nasopharyngeal carcinoma cell CNE1. We found that grifolin increased both Ser392 and Ser20 phosphorylation levels of transcription factor p53 protein, which could promote its transcriptional activity. Moreover, induced by grifolin, the recruitment of p53 to dapk1 gene promoter was confirmed to enhance markedly using EMSA and ChIP assays analysis. The involvement of DAPK1 in grifolin-induced apoptosis was supported by the studies that introducing siRNA targeting DAPK1 to CNE1 cells remarkably interfered grifolin-caused apoptotic effect as well as the activation of caspase-3. Grifolin induced upregulation of DAPK1 via p53 was also observed in tumour cells derived from human breast cancer and human colon cancer. The findings suggest that upregulation of DAPK1 via p53-DAPK1 pathway is an important mechanism of grifolin contributing to its ability to induce apoptotic effect. Since growing evidence found a significant loss of DAPK1 expression in a large variety of tumour types, grifolin may represent a promising candidate in the intervention of cancer via targeting DAPK1. (C) 2010 Elsevier Ltd. All rights reserved.
关键词Grifolin Mushroom Dapk1 P53 Apoptosis
资助信息National Natural Science Fund of China[90813028, 30801387]; Ministry of Science and Technology[2009CB522300]
学科领域Oncology
DOI10.1016/j.ejca.2010.09.021
收录类别SCI
语种英语
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000286715800019
引用统计
被引频次:31[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/151853/5329
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.Cent S Univ, Xiangya Sch Med, Canc Res Inst, Changsha 410078, Hunan, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resource W China, Kunming 650204, Yunnan, Peoples R China
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Luo, Xiang-jian,Li, Li-li,Deng, Qi-pan,et al. Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells[J]. EUROPEAN JOURNAL OF CANCER,2011,47(2):316-325.
APA Luo, Xiang-jian.,Li, Li-li.,Deng, Qi-pan.,Yu, Xin-fang.,Yang, Li-fang.,...&Cao, Ya.(2011).Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells.EUROPEAN JOURNAL OF CANCER,47(2),316-325.
MLA Luo, Xiang-jian,et al."Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells".EUROPEAN JOURNAL OF CANCER 47.2(2011):316-325.
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