Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly e...Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly expressed in the villous syncytiotrophoblasts but not in the cytotrophoblasts.The immunoreactive intensity for EGF-R decreased with the development of pregnancy.Concerning the intermediate trophoblasts in cell islands and cell columns,both proteins were more easily detected in the cells distal to the villous stroma than in the juxtastromal cells.These findings suggest that EGF-R and C-erbB-2 may play a significant role in the induction and regulation of differentiated trophoblast function展开更多
The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator o...The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability.MDM2,p53,and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer.Natural products,especially those from medicinal and food plants,are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers.Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers.In contrast to synthetic small-molecule MDM2 inhibitors,the majority of which have been designed to inhibit MDM2-p53 binding and activate p53,many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability,exerting their anticancer activity in both p53-dependent and p53-independent manners.More recently,several natural products have been reported to target mutant p53 in cancer.Therefore,identification of natural products targeting MDM2,mutant p53,and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents.In this review,we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway,emphasizing several emerging issues,such as the efficacy,mechanism of action,and specificity of these natural products.展开更多
文摘Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly expressed in the villous syncytiotrophoblasts but not in the cytotrophoblasts.The immunoreactive intensity for EGF-R decreased with the development of pregnancy.Concerning the intermediate trophoblasts in cell islands and cell columns,both proteins were more easily detected in the cells distal to the villous stroma than in the juxtastromal cells.These findings suggest that EGF-R and C-erbB-2 may play a significant role in the induction and regulation of differentiated trophoblast function
基金supported by National Institutes of Health(NIH)/National Cancer Institute(NCI)grants(R01 CA186662 and R01 CA214019 to RZ).The content is solely the responsibility of the authors,and does not necessarily represent the official views of the National Institutes of Health.supported by American Cancer Society(ACS)grant RSG-15-009-01-CDDsupported by funds for the Robert L.Boblitt Endowed Professor in Drug Discovery and research funds from the College of Pharmacy and the University of Houston+3 种基金supported by grants from the National Nature Science Foundation(81630086,81427805,81672763,31401611,and 81502122)the Key Research Program(ZDRW-ZS-2017-1)the Strategic Priority Research Program(XDA12020319)of the Chinese Academy of Sciencesthe Science and Technology Commission of Shanghai Municipality(16391903700 and 14391901800).
文摘The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability.MDM2,p53,and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer.Natural products,especially those from medicinal and food plants,are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers.Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers.In contrast to synthetic small-molecule MDM2 inhibitors,the majority of which have been designed to inhibit MDM2-p53 binding and activate p53,many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability,exerting their anticancer activity in both p53-dependent and p53-independent manners.More recently,several natural products have been reported to target mutant p53 in cancer.Therefore,identification of natural products targeting MDM2,mutant p53,and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents.In this review,we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway,emphasizing several emerging issues,such as the efficacy,mechanism of action,and specificity of these natural products.
