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.
Tumour Biol
; 37(8): 10653-64, 2016 Aug.
Article
en En
| MEDLINE
| ID: mdl-26867767
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_other_respiratory_diseases
/
6_trachea_bronchus_lung_cancer
Asunto principal:
Autofagia
/
Colchicina
/
Senescencia Celular
/
Neoplasias Pulmonares
/
Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
Tumour Biol
Asunto de la revista:
NEOPLASIAS
Año:
2016
Tipo del documento:
Article
País de afiliación:
India