AI Article Synopsis

  • Cancer treatment faces challenges like metastasis, angiogenesis, and drug resistance, with the methylation status of certain genes, particularly MMP-3, seen as key targets.
  • This study explores the effects of chemotherapeutic agents like methotrexate, paclitaxel, and cisplatin on MMP-3 gene promoter methylation and overall cell viability using assays.
  • Results show that while methotrexate and paclitaxel lead to increased methylation of the MMP-3 promoter, cisplatin results in unmethylation, suggesting that lowering drug doses while retaining effectiveness could improve treatment outcomes and patient quality of life.

Article Abstract

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 IC 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.

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Source
http://dx.doi.org/10.1007/s11033-020-05955-wDOI Listing

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