Institute of Biochemistry and Biophysics (I.B.B.), University of Tehran, Tehran, Iran.
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.
Chem Biol Interact. 2015 Aug 5;238:151-60. doi: 10.1016/j.cbi.2015.06.023. Epub 2015 Jun 20.
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.
西红花中的一种成分藏红花醛具有抗肿瘤活性，但这种作用的确切机制仍不清楚。在这项研究中，我们研究了藏红花醛存在时微管的组装和结构，以期通过微管功能障碍为藏红花醛作为抗肿瘤药物的潜力开辟新的视野。通过浊度法和透射电子显微镜（TEM）评估藏红花醛的抗微管活性。将藏红花醛（0.1-70μM）与微管蛋白（5μM）孵育，并通过荧光法测量微管蛋白结构的变化。通过分子对接估计藏红花醛与微管蛋白的结合位点。微管蛋白聚合在藏红花醛存在下显著降低，无论其浓度如何，IC50 值为 72.19μM。藏红花醛位于α和β微管蛋白之间，更靠近α微管蛋白，并与 Gly 142 形成氢键，疏水力在藏红花醛分子在结合位点的稳定中起着关键作用。藏红花醛可能通过α和β微管蛋白之间的结合导致微管蛋白组装减少，从而导致微管蛋白结构发生变化，其结合自由能为-5.63kcal/mol。藏红花醛可以被视为一种抗癌药物；然而，需要进行体内实验来证实这一结论。
