Valproic acid modulates radiation-enhanced matrix metalloproteinase activity and invasion of breast cancer cells
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
Purpose: To evaluate matrix metalloproteinase (MMP) activity and invasion after ionizing radiation (IR) exposure and to determine whether MMP could be epigenetically modulated by histone deacetylase (HDAC) inhibition. Material and methods: Two human breast cancer cell lines (MDA-MB-231 and MCF-7) were cultured in monolayer (2D) and in laminin-rich extracellular matrix (3D). Invasion capability, collagenolytic and gelatinolytic activity, MMP and TIMP protein and mRNA expression and clonogenic survival were analyzed after IR exposure, with and without a HDAC inhibition treatment [1.5 mM valproic acid (VA) or 1 μM trichostatin-A (TSA)]. Results: IR exposure resulted in cell line-dependent stimulation of invasion capacity. In contrast to MCF-7 cells, irradiated MDA-MB-231 showed significantly enhanced mRNA expression of mmp-1, mmp-3 and mmp-13 and of their regulators timp-1 and timp-2 relative to unirradiated controls. This translated into increased collagenolytic and gelatinolytic activity and could be reduced after valproic acid (VA) treatment. Additionally, VA also mitigated IR-enhanced mmp and timp mRNA expression as well as IR-increased invasion capability. Finally, our data confirm the radiosensitizing effect of VA. Conclusion: These results suggest that IR cell line-dependently induces upregulation of MMP mRNA expression, which appears to be mechanistically linked to a higher invasion capability that is modifiable by HDAC inhibition.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 946-956 |
Seitenumfang | 11 |
Fachzeitschrift | International journal of radiation biology |
Jahrgang | 91 |
Ausgabenummer | 12 |
Publikationsstatus | Veröffentlicht - 2 Dez. 2015 |
Peer-Review-Status | Ja |
Externe IDs
PubMed | 26490761 |
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ORCID | /0000-0001-5684-629X/work/162845938 |
Schlagworte
Ziele für nachhaltige Entwicklung
ASJC Scopus Sachgebiete
Schlagwörter
- breast cancer, epigenetic regulation, histone deacetylases, invasion, ionizing radiation, Matrix metalloproteinases, tumour microenvironment