Grifolin,a potential antitumor natural product from the mushroom Albatrellus confluens,upregulated Death-associated protein kinase 1(DAPK1)via p53-DAPK1 pathway as a central mechanism for apoptosis in nasopharyngeal carcinoma cells
会议名称：《中国病理生理学会受体、肿瘤和免疫专业委员会联合学术会议》
会议日期：2010年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：Grifolin DAPK1 p53-DAPK1
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 by our ***,the mechanisms of action are not completely understood.A 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 ***,we further investigated the role of DAPK1 in apoptotic effect induced by grifolin in nasopharyngeal carcinoma ***:RT-PCR and Western blot analysis were used to evaluate DAPK1 expression at mRNA and protein level,*** the basis of detection of p53 phosphorylation level,ChIP and EMSA assays were further applied to examine the recruitment of p53 to dapk1 gene promoters induced by *** and Flow Cytometry were introduced to denmonstrate the essential role of DAPK1 in the apoptotic effect induced by ***:We observed that protein as well as mRNA level of DAPK1 was induced by grifolin in a dose-dependent manner in nasopharyngeal carcinoma cell *** further found that grifolin increased both Ser392 and Ser20 phosphorylation levels of transcription factor p53 protein,which could promote its transcription ***,induced by grifolin,the recruitment of p53 to dapk1 gene promoters was confirmed to enhance markedly using ChIP and EMSA assays *** 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 ***:The findings suggest that upregulation of DAPK1 via p53-DAPK1 pathway is the main mechanism of grifolin contributing to its ability to induce apoptotic effect in nasopharyngeal carcinoma *** growing evidence