Anticancer activity,calf thymus DNA and human serum albumin binding properties of Farnesiferol C from Ferula pseudalliacea |
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Authors: | Hamid Tanzadehpanah Hanie Mahaki Pouria Samadi Jamshid Karimi Neda Hosseinpour Moghadam Sadegh Salehzadeh |
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Affiliation: | 1. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;2. Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;3. Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;4. Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran |
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Abstract: | In this study, Farnesiferol C was introduced as an anti-colon cancer agent. Its cytotoxicity was investigated on two cancer cell lines, HCT116 and CT26, and mesenchymal stem cells (MSCs) as normal cells employing MTT assay. Moreover, Farnesiferol C interactions with ct-DNA and HSA were investigated by various techniques. The IC50 values of Farnesiferol C on HCT116 and CT26 cells were 42 and 46?μM, respectively, while its IC50 value on MSCs cells was 92?μM, indicating that Farnesiferol C was more efficacious against cancer cell lines than normal cells. DNA competitive binding studies, viscosity and zeta potential measurements confirmed that Farnesiferol C bound to DNA through intercalation binding. HSA binding investigations revealed that there were two different binding sites for Far C on HSA with higher binding affinity in site 2 compared to site 1. Furthermore, Farnesiferol C could bind to HSA and quench its intrinsic fluorescence in a static quenching mechanism, with a distance of 2.54?nm. Competitive binding in the presence of warfarin and ibuprofen was carried out and the resulting quenching constant was strongly changed in the presence of warfarin. Consequently, Farnesiferol C most probably will be located within sub-domain IIA. In this study, molecular modeling buttressed and confirmed our laboratory results. Conclusively, we proposed that DNA is an appropriate target for Farnesiferol C. Therefore, Farnesiferol C and its semisynthetic analogues can be one of the priority innovations in research on anticancer drugs. |
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Keywords: | MTT assay HSA Ct-DNA Fluorescence spectroscopy Zeta potential Molecular modeling |
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