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
Corresponding AuthorLiu, JK (reprint author), Cent S Univ, Xiangya Sch Med, Canc Res Inst, Changsha 410078, Hunan, Peoples R China
2011
Source PublicationEUROPEAN JOURNAL OF CANCER
ISSN0959-8049
Volume47Issue:2Pages:316-325
AbstractGrifolin, 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.
KeywordGrifolin Mushroom Dapk1 P53 Apoptosis
Subject AreaOncology
DOI10.1016/j.ejca.2010.09.021
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000286715800019
Citation statistics
Cited Times:33[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/5329
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.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
Recommended Citation
GB/T 7714
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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