Mithramycin exerts an anti-Myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors

Eleonore Otjacques, Marilene Binsfeld, Natacha Rocks, Silvia Blacher, Karin Vanderkerken, Agnes Noel, Yves Beguin, Didier Cataldo, Jo Caers

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Mithramycin (MTM), a cytotoxic compound, is currently being investigated for its anti-angiogenic activity that seems to be mediated through an inhibition of the transcription factor SP1. In this study we evaluated its anti-myeloma effects in the syngenic 5TGM1 model in vitro as well as in vivo. In vitro, MTM inhibited DNA synthesis of 5TGM1 cells with an IC50 of 400 nM and induced an arrest in cell cycle progression at the G1/S transition point. Western-blot revealed an up-regulation of p53, p21 and p27 and an inhibition of c-Myc, while SP1 remained unaffected. In rat aortic ring assays, a strong antiangiogenic effect was seen, which could be explained by a decrease of VEGF production and an up regulation of antiangiogenic proteins such as IP10 after MTM treatment. The administration of MTM to mice injected with 5TGM1 decreased 5TGM1 cell invasion into bone marrow and myeloma neovascularisation. These data suggest that MTM displays antimyeloma and anti-angiogenic effects that are not mediated by an inhibition of SP1 but rather through c-Myc inhibition and p53 activation.
Original languageEnglish
Article numbere62818
Number of pages11
JournalPLoS ONE
Volume8
Issue number5
Publication statusPublished - 7 May 2013

Keywords

  • myeloma

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