title: Novel mithramycins abrogate the involvement of protein factors in the transcription of cell cycle control genes.
abstract: The effects of mithramycin SK (MSK) and demycarosyl-3D-β-D-digitoxosyl-mithramycin SK (DIG-MSK; EC-8042), two novel analogs of the antitumor antibiotic mithramycin A, on gene transcription were examined in human HCT116 colon carcinoma cells by quantitative real-time PCR of 89 genes mainly involved in cell cycle control. Each one of the analogs down-regulated a different set of genes, while only five genes were down-regulated by both compounds. Moreover, other genes were significantly up-regulated, among them p21(WAF1)/CDKN1A which is involved in halting cells at the G1 and G2/M checkpoints. These results are rationalized in terms of MSK or DIG-MSK competition with various transcription factors for binding to consensus C/G-rich tracts encompassed in gene promoters. Changes in cell cycle distribution and protein levels after treatment with every analog were consistent with changes observed in gene expression.
authors.affiliation: Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vizcaíno
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mansilla
authors.forename: Luz-Elena
authors.initials: LE
authors.lastname: Núñez
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
authors.forename: Francisco
authors.initials: F
authors.lastname: Morís
authors.forename: José
authors.initials: J
authors.lastname: Portugal
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001665:Binding Sites; D059585:G1 Phase Cell Cycle Checkpoints; D059565:G2 Phase Cell Cycle Checkpoints; D018816:Genes, cdc; D045325:HCT116 Cells; D006801:Humans; D009336:Necrosis; D008926:Plicamycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014157:Transcription Factors; C576677:demycarosyl-3D-digitoxosylmithramycin SK; C520007:mithramycin SK; D008926:Plicamycin