Epigenetic modulators combination with chemotherapy in breast cancer cells.

Ari F., Napieralski R., Akgun O., Magdolen V., Ulukaya E.

Cell biochemistry and function, cilt.39, ss.571-583, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 39
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/cbf.3626
  • Dergi Adı: Cell biochemistry and function
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.571-583
  • Anahtar Kelimeler: breast cancer, DNA&#8208, methylation, epigenetic modulators, HDAC&#8208, inhibitor, HISTONE DEACETYLASE INHIBITOR, PITX2 DNA-METHYLATION, TRANS-RETINOIC ACID, LOW-DOSE DECITABINE, VALPROIC ACID, GENE-EXPRESSION, PLASMINOGEN-ACTIVATOR, ADJUVANT CHEMOTHERAPY, CISPLATIN RESISTANCE, CLINICAL VALIDATION
  • Bursa Uludağ Üniversitesi Adresli: Evet

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.