title: α-Cyclodextrin Interacts Close to Vinblastine Site of Tubulin and Delivers Curcumin Preferentially to the Tubulin Surface of Cancer Cell.
abstract: 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.
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Batakrishna
authors.initials: B
authors.lastname: Jana
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Saswat
authors.initials: S
authors.lastname: Mohapatra
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Mondal
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Barman
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Krishnangsu
authors.initials: K
authors.lastname: Pradhan
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Saha
authors.affiliation: Organic & Medicinal Chemistry Division, and ‡Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D062105:Molecular Docking Simulation; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D014747:Vinblastine / Q000378:metabolism; D047391:alpha-Cyclodextrins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D047391:alpha-Cyclodextrins; D014747:Vinblastine; D003474:Curcumin
keywords: cancer cell; curcumin delivery; spheroid; tubulin/microtubule; α-cyclodextrin