title: Euphohelioscopin A is a PKC activator capable of inducing macrophage differentiation.
abstract: To identify small molecules that selectively control hematopoietic stem cell differentiation, we performed an unbiased screen using primary human CD34(+) cells. We identified a plant-derived natural product, euphohelioscopin A, capable of selectively differentiating CD34(+) cells down the granulocyte/monocytic lineage. Euphohelioscopin A also inhibits proliferation and induces differentiation of the myeloid leukemia cell lines THP-1 and HL-60. Mechanistic studies revealed that euphohelioscopin A is an activator of protein kinase C (PKC), and that the promonocytic effects of this natural product are mediated by PKC activation. In addition to shedding insights into normal hematopoiesis, this work may ultimately facilitate the application of stem cell therapies to a host of myeloid dysfunctions.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: de Lichtervelde
authors.forename: Corina E
authors.initials: CE
authors.lastname: Antal
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Boitano
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Philipp
authors.initials: P
authors.lastname: Krastel
authors.forename: Frank
authors.initials: F
authors.lastname: Petersen
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Newton
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cooke
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D057809:HEK293 Cells; D018922:HL-60 Cells; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; D018952:Antigens, CD34; D004224:Diterpenes; D007211:Indoles; D008301:Maleimides; C576841:euphohelioscopin A; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate