title: Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy.
abstract: Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of colchicine against cancer is limited by its toxicity against normal cells. But, there is no report of its cytotoxic potential against lung cancer cell, at clinically permissible or lower concentrations, minimally toxic to non-cancerous cells. Hence, in the present study, we investigated the possible mechanism by which the efficacy of colchicine against lung cancer cells at less toxic dose could be enhanced. Colchicine at clinically admissible concentration of 2.5 nM had no cytotoxic effect and caused no G2/M arrest in A549 cells. However, at this concentration, colchicine strongly hindered the reformation of cold depolymerised interphase and spindle microtubule. Colchicine induced senescence and reactive oxygen species mediated autophagy in A549 cells at this concentration. Autophagy inhibitor 3-methyladenine (3-MA) sensitised the cytotoxicity of colchicine in A549 cells by switching senescence to apoptotic death, and this combination had reduced cytotoxicity to normal lung fibroblast cells (WI38). Together, these findings indicated the possible use of colchicine at clinically relevant dose along with autophagy inhibitor in cancer therapy.
authors: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB, 700 019, India.
authors: Surela
authors: S
authors: Bhattacharya
authors: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB, 700 019, India.
authors: Amlan
authors: A
authors: Das
authors: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB, 700 019, India.
authors: Satabdi
authors: S
authors: Datta
authors: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB, 700 019, India.
authors: Arnab
authors: A
authors: Ganguli
authors: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, WB, 700 019, India. gcbcg@caluniv.ac.in.
authors: Gopal
authors: G
authors: Chakrabarti
mesh_terms: D000072283:A549 Cells; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D003078:Colchicine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; C025946:3-methyladenine; D000225:Adenine; D003078:Colchicine
keywords: Autophagy; Colchicine; Lung cancer; Microtubule; ROS