3-chloromethylene-6-fluorothiochroman-4-one, A novel DNA Topoisomerase poison
| Autor: | Yitian, Wang, Juntao, Chen, Rui, Shen, Chunliu, Yang, Zhengyue, Ma, Yuxin, Liu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Dose-Response Relationship
Drug Cell Survival Uterine Cervical Neoplasms Apoptosis DNA Neoplasm DNA-Binding Proteins DNA Topoisomerases Type II DNA Topoisomerases Type I Isomerism Antigens Neoplasm Chromones Humans Nucleic Acid Conformation Topoisomerase II Inhibitors Female Chromans Topoisomerase I Inhibitors DNA Damage HeLa Cells |
| Zdroj: | Pakistan journal of pharmaceutical sciences. 29 |
| ISSN: | 1011-601X |
| Popis: | 3-Chloromethylene-6-fluorothiochroman-4-one (CMFT) is a novel thiochromanones derivative that has better anti-tumor activity. In this paper, we will compare the antitumor activity of the cis-trans isomers, and explore their inhibiting effects on human topoisomerase I and topoisomerase II in cell free reaction system. The MTT method was used to study inhibition rates; the AO/EB double staining and TUNEL assay was used to assess proportion of apoptotic cells. The inhibition of CMFT to Topo I and II could be identified by adding CMFT solutions to Topo-DNA reaction mixtures and observing the relative quantities of relaxed strands and supercoils in electrophoresis assay. Results showed that CMFT had dramatic anti-tumor activities at low concentrations and the activity of CMFT trans-isomer is more significant. Use of AO/EB double staining and TUNEL indicated that CMFT induces apoptosis. DNA relaxation assays and DNA cleavage and relegation assays were performed and showed a higher potential to interact with topoisomerase I (Topo I) and topoisomerase II (Topo II) and it was verified that CMFT is a Topo poison which could be one of the mechanisms that induce cell apoptosis. Our results provide preliminary data for further investigation for the mechanism of CMFT of the apoptotic mechanism. |
| Databáze: | OpenAIRE |
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