Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors.
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 v...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3646989?pdf=render |
| _version_ | 1818196055893737472 |
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| author | Eléonore Otjacques Marilène Binsfeld Natacha Rocks Silvia Blacher Karin Vanderkerken Agnès Noel Yves Beguin Didier Cataldo Jo Caers |
| author_facet | Eléonore Otjacques Marilène Binsfeld Natacha Rocks Silvia Blacher Karin Vanderkerken Agnès Noel Yves Beguin Didier Cataldo Jo Caers |
| author_sort | Eléonore Otjacques |
| collection | DOAJ |
| description | 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 anti-angiogenic effect was seen, which could be explained by a decrease of VEGF production and an up-regulation of anti-angiogenic 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 anti-myeloma and anti-angiogenic effects that are not mediated by an inhibition of SP1 but rather through c-Myc inhibition and p53 activation. |
| first_indexed | 2024-12-12T01:28:00Z |
| format | Article |
| id | doaj.art-2c620ebc25d046f2b9432fad6aeac081 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T01:28:00Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2c620ebc25d046f2b9432fad6aeac0812022-12-22T00:43:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6281810.1371/journal.pone.0062818Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors.Eléonore OtjacquesMarilène BinsfeldNatacha RocksSilvia BlacherKarin VanderkerkenAgnès NoelYves BeguinDidier CataldoJo CaersMithramycin (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 anti-angiogenic effect was seen, which could be explained by a decrease of VEGF production and an up-regulation of anti-angiogenic 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 anti-myeloma and anti-angiogenic effects that are not mediated by an inhibition of SP1 but rather through c-Myc inhibition and p53 activation.http://europepmc.org/articles/PMC3646989?pdf=render |
| spellingShingle | Eléonore Otjacques Marilène Binsfeld Natacha Rocks Silvia Blacher Karin Vanderkerken Agnès Noel Yves Beguin Didier Cataldo Jo Caers Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors. PLoS ONE |
| title | Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors. |
| title_full | Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors. |
| title_fullStr | Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors. |
| title_full_unstemmed | Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors. |
| title_short | Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors. |
| title_sort | mithramycin exerts an anti myeloma effect and displays anti angiogenic effects through up regulation of anti angiogenic factors |
| url | http://europepmc.org/articles/PMC3646989?pdf=render |
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