title: Safranal as a novel anti-tubulin binding agent with potential use in cancer therapy: An in vitro study.
abstract: Safranal, a component of saffron, indicates anti-tumor activities; however, the precise mechanism of this effect has remained elusive. In this study we investigated tubulin assembly and structure in the presence of safranal to open the new horizons about the potential of safranal as an anti-tumor agent via microtubule disfunction. Anti-microtubule activity of safranal was evaluated by turbidimetric method and transmission electron microscopy (TEM). Safranal (0.1-70μM) was incubated with tubulin (5μM) and tubulin structural changes was surveyed using fluorometry. Tubulin binding site with safranal was estimated by molecular docking. Microtubule polymerization decreased significantly in the presence of safranal, regardless of its concentration and the IC50 value was obtained 72.19μM. Safranal was situated between α and β tubulin closer to α-tubulin and hydrogen bond with Gly 142 and hydrophobic interactions played critical roles for safranal molecule stabilization in binding site. It seems that decline of tubulin assembly could result from tubulin structural changes through safranal bindings between alpha and beta tubulin with ΔG(0) of -5.63kcal/mol. Safranal can be taken into account as an anticancer agent; however, in vivo experiments are required to confirm this conclusion.
authors.affiliation: Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Naghshineh
authors.affiliation: Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Dadras
authors.affiliation: Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran; Department of Medical Nanotechnology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Behafarid
authors.initials: B
authors.lastname: Ghalandari
authors.affiliation: Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran. Electronic address: riazi@ut.ac.ir.
authors.forename: Gholam Hossein
authors.initials: GH
authors.lastname: Riazi
authors.affiliation: Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran; Department of Biological Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Seyed Mohamad Sadegh
authors.initials: SM
authors.lastname: Modaresi
authors.affiliation: Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Afrasiabi
authors.affiliation: Department of Microbiology, Faculty of Science, Islamic Azad University, Karaj, Iran.
authors.forename: Mahsa Kiani
authors.initials: MK
authors.lastname: Aslani
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D053138:Cyclohexenes / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008870:Microtubules / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012756:Sheep; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000378:metabolism
chemical_list: D053138:Cyclohexenes; D013729:Terpenes; D014404:Tubulin; D050257:Tubulin Modulators; C087963:safranal
keywords: Anticancer agent; Microtubule; Saffron; Safranal; Tubulin structure