Alterations in the matrix metalloproteinase-3 promoter methylation after common chemotherapeutics: in vitro study of paclitaxel, cisplatin and methotrexate in the MCF-7 and SH-SY5Y cell lines
| Autor: | Fatma Nihan Cankara, Caner Günaydın, Zülfinaz Betül Çelik |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Paclitaxel Cell Survival Angiogenesis Antineoplastic Agents Inhibitory Concentration 50 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Genetics medicine Humans Viability assay Epigenetics Promoter Regions Genetic Molecular Biology Cisplatin Dose-Response Relationship Drug Chemistry Drug Synergism General Medicine Methylation DNA Methylation Methotrexate 030104 developmental biology MCF-7 030220 oncology & carcinogenesis Cancer cell MCF-7 Cells Cancer research Matrix Metalloproteinase 3 medicine.drug |
| Zdroj: | Molecular Biology Reports. 47:8987-8995 |
| ISSN: | 1573-4978 0301-4851 |
| Popis: | Cancer treatment is a complex process due to the several encountered obstacles during therapy, such as metastasis, angiogenesis, and drug resistance. The methylation status of elements that are thought to play crucial roles in these mechanisms is considered valuable targets. Matrix metalloproteinase-3 (MMP-3), one of the possible targets, is a well-known endopeptidase and secreted by several types of cancer cells. Paclitaxel, cisplatin, and methotrexate are frequently used for several malignancies, individually or in combination. Therefore, the aims of this study is that demonstration of possible effects of different doses of single or jointly application of these agents with maintaining their antiproliferative activity in clinically relevant cell lines, as well as revealing epigenetic results of this pharmacological alteration with exploring promoter methylation status of the MMP-3 gene. Cell viability was determined with Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Further methylation-specific PCR (MSP) experiments for determining the promoter methylation status of MMP-3 were performed according to the obtained IC50 values of the drug treatments. The MMP-3 promoter methylation status was analayzed with MSP and determined with agarose gel electrophoresis. As a result, methotrexate and paclitaxel treatment significantly methylated the MMP-3 promoter; however, cisplatin caused MMP-3 promoter unmethylation in MCF-7 and SH-SY5Y cells. Our study indicates that decreasing the dose of clinically prevalent chemotherapeutic agents while maintaining the same tumor-killing potency might be a rational strategy for treatment. In addition to avoiding adverse effects of these compounds, decreasing treatment doses will bring substantial benefits for patient life-quality. |
| Databáze: | OpenAIRE |
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