Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-08

AUTHORS

Surela Bhattacharya, Amlan Das, Satabdi Datta, Arnab Ganguli, Gopal Chakrabarti

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. More... »

PAGES

10653-10664

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13277-016-4972-7

DOI

http://dx.doi.org/10.1007/s13277-016-4972-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017908628

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26867767


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