Anticancer activity, calf thymus DNA and human serum albumin binding properties of Farnesiferol C from Ferula pseudalliacea

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.

KEYWORDS::

• MTT assay
• HSA
• Ct-DNA
• Fluorescence spectroscopy
• Zeta potential
• Molecular modeling

Acknowledgment

The authors would like to acknowledge the Research Center of Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is a part of research project and was financially supported by Deputy of Research, Hamadan University of Medical Sciences [grant number 9612158167]. Therefore, the authors are very thankful for the support of this deputy.