α-Cyclodextrin Interacts Close to Vinblastine Site of Tubulin and Delivers Curcumin Preferentially to the Tubulin Surface of Cancer Cell

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• 作者：Batakrishna Jana ; Saswat Mohapatra ; Prasenjit Mondal ; Surajit Barman ; Krishnangsu Pradhan ; Abhijit Saha ; Surajit Ghosh
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：June 8, 2016
• 年：2016
• 卷：8
• 期：22
• 页码：13793-13803
• 全文大小：575K
• 年卷期：0
• ISSN：1944-8252

文摘

Tubulin is the key cytoskeleton component, which plays a crucial role in eukaryotic cell division. Many anticancer drugs have been developed targeting the tubulin surface. Recently, it has been shown that few polyhydroxy carbohydrates perturb tubulin polymerization. Cyclodextrin (CD), a polyhydroxy carbohydrate, has been extensively used as the delivery vehicle for delivery of hydrophobic drugs to the cancer cell. However, interaction of CD with intracellular components has not been addressed before. In this Article, we have shown for the first time that α-CD interacts with tubulin close to the vinblastine site using molecular docking and Förster resonance energy transfer (FRET) experiment. In addition, we have shown that α-CD binds with intracellular tubulin/microtubule. It delivers a high amount of curcumin onto the cancer cell, which causes severe disruption of intracellular microtubules. Finally, we have shown that the inclusion complex of α-CD and curcumin (CCC) preferentially enters into the human lung cancer cell (A549) as compared to the normal lung fibroblast cell (WI38), causes apoptotic death, activates tumor suppressor protein (p53) and cyclin-dependent kinase inhibitor 1 (p21), and inhibits 3D spheroid growth of cancer cell.