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Novel mithramycins abrogate the involvement of protein factors in the transcription of cell cycle control genes

AuthorsVizcaíno, Carolina ; Mansilla, Sylvia ; Méndez, Carmen; Salas, José A.; Portugal, José
KeywordsMithramycin SK
Antitumor drugs
Transcription factors
Issue Date2012
CitationBiochemical Pharmacology 84(9): 1133-1142 (2012)
AbstractThe 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. © 2012 Elsevier Inc. All rights reserved.
Identifiersdoi: 10.1016/j.bcp.2012.08.003
issn: 0006-2952
e-issn: 1873-2968
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