PMID- 33136246 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20210524 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 47 IP - 11 DP - 2020 Nov TI - 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. PG - 8987-8995 LID - 10.1007/s11033-020-05955-w [doi] AB - 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(50) 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. FAU - Celik, Zulfinaz Betul AU - Celik ZB AUID- ORCID: 0000-0003-1390-7309 AD - Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, 55270, Samsun, Turkey. betul.celik@omu.edu.tr. FAU - Cankara, Fatma Nihan AU - Cankara FN AUID- ORCID: 0000-0002-2367-6412 AD - Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, 32260, Isparta, Turkey. FAU - Gunaydin, Caner AU - Gunaydin C AUID- ORCID: 0000-0002-8304-832X AD - Department of Pharmacology, Faculty of Medicine, Ondokuz Mayis University, 55270, Samsun, Turkey. LA - eng PT - Journal Article DEP - 20201102 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Antineoplastic Agents) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - P88XT4IS4D (Paclitaxel) RN - Q20Q21Q62J (Cisplatin) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Antineoplastic Agents/pharmacology MH - Cell Line, Tumor MH - Cell Survival/drug effects/genetics MH - Cisplatin/*pharmacology MH - DNA Methylation/*drug effects MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Humans MH - Inhibitory Concentration 50 MH - MCF-7 Cells MH - Matrix Metalloproteinase 3/*genetics MH - Methotrexate/*pharmacology MH - Paclitaxel/*pharmacology MH - Promoter Regions, Genetic/*genetics OTO - NOTNLM OT - Cisplatin OT - Matrix metalloproteinase-3 OT - Methotrexate OT - Methylation OT - Paclitaxel EDAT- 2020/11/03 06:00 MHDA- 2021/05/25 06:00 CRDT- 2020/11/02 12:11 PHST- 2020/07/07 00:00 [received] PHST- 2020/10/28 00:00 [accepted] PHST- 2020/11/03 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2020/11/02 12:11 [entrez] AID - 10.1007/s11033-020-05955-w [pii] AID - 10.1007/s11033-020-05955-w [doi] PST - ppublish SO - Mol Biol Rep. 2020 Nov;47(11):8987-8995. doi: 10.1007/s11033-020-05955-w. Epub 2020 Nov 2.