Yayın: Epigenetic modulators combination with chemotherapy in breast cancer cells
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Tarih
2021-02-20
Kurum Yazarları
Akgün, Oğuzhan
Yazarlar
Arı, Ferda
Napieralski, Rudolf
Akgün, Oğuzhan
Magdolen, Viktor
Ulukaya, Engin
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayımcı
Wiley
Özet
Despite the concerning adverse effects on tumour development, epigenetic drugs are very promising in cancer treatment. The aim of this study was to compare the differential effects of standard chemotherapy regimens (FEC: 5-fluorouracil plus epirubicine plus cyclophosphamide) in combination with epigenetic modulators (decitabine, valproic acid): (a) on gene methylation levels of selected tumour biomarkers (LINE-1, uPA, PAI-1, DAPK); (b) their expression status (uPA and PAI-1); (c) differentiation status (5meC and H3K27me3). Furthermore, cell survival as well as changes concerning the invasion capacity were monitored in cell culture models of breast cancer (MCF-7, MDA-MB-231). A significant overall decrease of cell survival was observed in the FEC-containing combination therapies for both cell lines. Methylation results showed a general tendency towards increased demethylation of the uPA and PAI-1 gene promoters for the MCF-7 cells, as well as the proapoptotic DAPK gene in the treatment regimens for both cell lines. The uPA and PAI-1 antigen levels were mainly increased in the supernatant of FEC-only treated MDA-MB-231 cells. DAC-only treatment induced an increase of secreted uPA protein in MCF-7 cell culture, while most of the VPA-containing regimens also induced uPA and PAI-1 expression in MCF-7 cell fractions. Epigenetically active substances can also induce a re-differentiation in tumour cells, as shown by 5meC, H3K27me3 applying ICC.Significance of the study Epigenetic modulators especially in the highly undifferentiated and highly malignant MDA-MB-231 tumour cells significantly reduced tumour malignancy thus; further clinical studies applying specific combination therapies with epigenetic modulators may be warranted.
Açıklama
Anahtar kelimeler
Histone deacetylase inhibitor, Pitx2 dna-methylation, Trans-retinoic acid, Low-dose decitabine, Valproic acid, Gene-expression, Plasminogen-activator, Adjuvant chemotherapy, Cisplatin resistance, Clinical validation, Breast cancer, Dna‐, Methylation, Epigenetic modulators, Hdac‐, Inhibitor, Science & technology, Life sciences & biomedicine, Biochemistry & molecular biology, Cell biology