title: Lidamycin induces neural differentiation of mouse embryonic carcinoma cells through down-regulation of transcription factor Oct4.
abstract: Lidamycin is a potential anti-cancer drug, which is widely used in a variety of human cancer types. It has been reported that lidamycin inhibited mouse embryonic carcinoma (EC) cells growth through down-regulation of embryonic stem (ES) cell-like genes. In this study, whether 0.01 nM lidamycin induces neuronal differentiation of mouse EC cells was investigated. It was observed that lidamycin decreased transcription factor Oct4, and increased both p21 mRNA and protein expression in P19 EC cells. Furthermore, luciferase assay showed that lidamycin activated p21 promoter activity through suppression of Oct4, and Chromatin immunoprecipitation (ChIP) assay confirmed that binding of transcription factor Oct4 to the p21 promoter decreased in lidamycin-exposed cells. Knockdown of Oct4 resulted in neuron-like differentiation and up-regulation of p21 expression. In accordance, overexpression of Oct4 blocked neural differentiation and down-regulated p21 in lidamycin-treated P19 cells. Taken together, these results suggested that neuronal differentiation of EC cells induced by lidamycin was associated with the inhibition of Oct4 expression and the activation of p21 transcription. Our results have provided a novel mechanism, in which lidamycin led to cancer cell differentiation.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Xue Yuan Road 38, Beijing 100191, PR China. hyzhen@bjmu.edu.cn
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Zhen
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Yao
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Liu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Ma
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018236:Carcinoma, Embryonal; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D053281:Enediynes / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D050814:Octamer Transcription Factor-3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053281:Enediynes; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C058024:C 1027