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

Biochem Pharmacol. 2012 Nov 1;84(9):1133-42. doi: 10.1016/j.bcp.2012.08.003. Epub 2012 Aug 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Binding Sites
  • G1 Phase Cell Cycle Checkpoints
  • G2 Phase Cell Cycle Checkpoints
  • Genes, cdc*
  • HCT116 Cells
  • Humans
  • Necrosis
  • Plicamycin / analogs & derivatives*
  • Plicamycin / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects


  • Antineoplastic Agents
  • Transcription Factors
  • demycarosyl-3D-digitoxosylmithramycin SK
  • mithramycin SK
  • Plicamycin