Induction of HRR genes and inhibition of DNMT1 is associated with anthracycline anti-tumor antibiotic-tolerant breast carcinoma cells
| Autor: | Md. Saimul Islam, Susanta Roychoudhury, Neyaz Alam, Hemantika Dasgupta, Chinmay Kumar Panda, Anup Roy |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
0301 basic medicine Anthracycline Clinical Biochemistry Breast Neoplasms Gene Expression Regulation Enzymologic 03 medical and health sciences 0302 clinical medicine medicine Humans Doxorubicin Viability assay Molecular Biology biology Recombinational DNA Repair Promoter DNA Neoplasm Cell Biology General Medicine Methylation DNA Methylation Neoplasm Proteins Proliferating cell nuclear antigen Gene Expression Regulation Neoplastic 030104 developmental biology Drug Resistance Neoplasm Nogalamycin Cell culture 030220 oncology & carcinogenesis MCF-7 Cells Cancer research DNMT1 biology.protein Female medicine.drug |
| Zdroj: | Molecular and Cellular Biochemistry. 453:163-178 |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-018-3442-5 |
| Popis: | The aim of the study was to understand the role of homologous recombination repair (HRR) pathway genes in development of chemotolerance in breast cancer (BC). For this purpose, chemotolerant BC cells were developed in MCF-7 and MDA MB 231 cell lines after treatment with two anthracycline anti-tumor antibiotics doxorubicin and nogalamycin at different concentrations for 48 h with differential cell viability. The drugs were more effective in MCF-7 (IC50: 0.214-0.242 µM) than in MDA MB 231 (IC50: 0.346-0.37 µM) as shown by cell viability assay. The drugs could reduce the protein expression of PCNA in the cell lines. Increased mRNA/protein expression of the HRR (BRCA1, BRCA2, FANCC, FANCD2, and BRIT1) genes was seen in the cell lines in the presence of the drugs at different concentrations (lower IC50, IC50, and higher IC50) irrespective of the cell viability (68-41%). Quantitative methylation assay showed an increased percentage of hypomethylation of the promoters of these genes after drug treatment in the cell lines. Similarly, chemotolerant neoadjuvant chemotherapy (NACT) treated primary BC samples showed significantly higher frequency of hypomethylation of the genes than the pretherapeutic BC samples. The drugs in different concentrations could reduce m-RNA and protein expression of DNMT1 (DNA methyltransferase 1) in the cell lines. Similar phenomenon was also evident in the NACT samples than in the pretherapeutic BC samples. Thus, our data indicate that reduced DNMT1 expression along with promoter hypomethylation and increased expression of the HRR genes might have importance in chemotolerance in BC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink