2024-03-29T06:57:00Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/247812018-08-29T07:42:46Zcom_10261_22com_10261_1col_10261_275
00925njm 22002777a 4500
dc
Martín-Duque, Pilar
author
Quintanilla, Miguel
author
McNeish, Iain
author
Lopes, Rita
author
Romero, Jesús
author
Romero, Diana
author
Ramón y Cajal, Santiago
author
Vassaux, Georges
author
2006-05
The cytotoxic effect of anticancer drugs has been shown to involve induction of apoptosis. This observation raises the possibility that factors affecting caspase activation might be important determinants of anticancer drug sensitivity. Ectopic expression of caspase-1 has been shown to trigger apoptosis. However, the role of caspase-1 in apoptosis is now considered as minor compared to other caspases. In patients, high levels of caspase-1 expression may be associated with spontaneous regression in neuroblastomas and with a good clinical response to chemotherapy in acute myeloid leukemia and osteosarcoma. In experimental therapeutics for cancer, caspase-1 has been related to some anticancer activity. These observations led us to examine the effect of over-expression on the response to chemotherapy and radiotherapy in vitro and in vivo. Caspase-1 expression mediated by an adenoviral vector was able to kill directly cells and to sensitise the remaining cells to cisplatin or γ-radiation in vitro. In HeLa cells stably transfected with caspase-1, sensitisation to cisplatin was due to an amplification of the cisplatin-induced mitochondrial apoptotic pathway activation. Caspase-1 mediated sensitisation to cisplatin and γ-radiation was also observed in vivo. Altogether, we conclude that caspase-1 can act as a radio- and chemo-sensitiser, in vitro and in vivo.
International Journal of Molecular Medicine 17(5): 841-847 (2006)
1107-3756
http://hdl.handle.net/10261/24781
16596269
Caspases
Sensitisation
Chemotherapy
Radiotherapy
Gene therapy
Caspase-1 as a radio- and chemo-sensitiser in vitro and in vivo