Journal
CELL BIOCHEMISTRY AND FUNCTION
Volume 29, Issue 8, Pages 651-659Publisher
WILEY
DOI: 10.1002/cbf.1801
Keywords
apoptosis; breast cancer; decitabine; DNA methylation; M30-antigen; PAI-1; uPA
Categories
Funding
- TUBITAK (The Scientific and Technical Research Council of Turkey) [106S349]
- Science and Technology Facilities Council [ST/G502347/1, ST/I005912/1, ST/I000410/1, ST/I005912/1 GRIDPP, ST/I002200/1, ST/F006748/1] Funding Source: researchfish
- STFC [ST/I000410/1, ST/F006748/1, ST/G502347/1, ST/I005912/1, ST/I002200/1] Funding Source: UKRI
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Epigenetic drugs are promising add-ons to cancer treatment; still, adverse effects concerning tumour promotion have been reported occasionally. In this in vitro study, we investigated the effect of combination treatment of decitabine with anthracycline-based chemotherapy [5-fluorouracil plus epirubicine plus cyclophosphamide (FEC)] on viability and metastatic activity of breast cancer cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). The effect of decitabine and its combined treatment with FEC on viability of both cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and adenosine triphosphate (ATP) cell survival assays. DNA methylation specific real-time polymerase chain reaction (PCR) (Methylight (R)) was employed to document the methylation status of the metastasis-relevant urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-I (PAI-1) genes. Additionally, protein expression levels of uPA and PAI-1 were determined using enzyme-linked immunosorbent assays. Invasion capacity of cells was assayed using Matrigel (R) invasion assay. Decitabine lowered the viability of MCF-7 cells, although MDA-MB-231 cells were not affected. Decitabine did not augment FEC-mediated cytotoxicity in both cell lines. In MCF-7 cells, methylation of the uPA and PAI-1 gene promoter was significantly reduced by decitabine or decitabine plus FEC. Protein levels of uPA and PAI-1 were induced by all treatments. Decitabine significantly induced the invasion capacity of MCF-7 cells, whereas all of the drugs resulted in decreased invasion capacity of MDA-MB-231. Our results suggest differential effects of single-dose decitabine and its combination with FEC on the metastatic capacity and survival of breast cancer cell lines endowed with different metastatic behaviour. Copyright (c) 2011 John Wiley & Sons, Ltd.
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