title: III-10, a newly synthesized flavonoid, induced differentiation of human U937 leukemia cells via PKCδ activation.
abstract: Flavonoid is an important group of natural products which exerted anticancer effects against various cancers. III-10 is a newly synthesized flavonoid with a pyrrolidinyl and a benzyl group substitution. It shares a same carbon skeleton with flavonoid which indicates that it may also have potential anticancer activity. To investigate whether III-10 could express anticancer effect on human U937 leukemia cells through differentiation induction, a series of experiments were processed. MTT and trypan-blue excluding assays showed that III-10 possessed growth and viability inhibition effects on U937 cells. Giemsa staining was implemented to observe the morphologic changes of U937 cells after III-10 treatment. Nitroblue tetrazolium (NBT) reduction assay and cell surface antigen flow cytometry were carried out to figure out the way III-10 induced U937 cells to differentiate. These experiments revealed that III-10 could induce U937 cells to differentiate into monocyte-like cells. Western blots and immunofluorescence were performed to inspect the possible underlying mechanism. The results revealed that differentiation-related proteins phospholipids scramblase 1 (PLSCR1) and promyelocytic leukemia protein (PML) were up-regulated after III-10 treatment. And III-10 stimulated PLSCR1 and PML probably through activation of protein kinase Cδ (PKCδ). All these results suggested that III-10 was a prospective anticancer compound and was requisite to be proceeded further investigation.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. qys0518@163.com
authors.forename: Yansu
authors.initials: Y
authors.lastname: Qin
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Hui
authors.forename: Yajing
authors.initials: Y
authors.lastname: Sun
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D051745:Protein Kinase C-delta / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D039481:CD11b Antigen; D047309:Flavones; D005419:Flavonoids; C574798:III-10; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D009687:Nuclear Proteins; C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; D000071156:Promyelocytic Leukemia Protein; D011759:Pyrrolidines; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D051745:Protein Kinase C-delta