Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line.
Int J Oncol
; 37(2): 463-71, 2010 Aug.
Article
en En
| MEDLINE
| ID: mdl-20596674
ABSTRACT
Etoposide (VP-16) is a topoisomerase-II (topo II) inhibitor chemotherapeutic agent. Studies have shown that a combination of VP-16 with other drugs demonstrates better clinical responses. The aim of this study was to investigate the effects of moxifloxacin (MXF) and VP-16 on cellular topo II activity in drug-treated cells and evaluate the influence of MXF on the mode of action of VP-16, on proliferation and apoptosis of HT-29 cells. Decatenation assay, band depletion and Western blot analysis, cytotoxic assay (MTT), flow cytometric studies (cell cycle and survivin expression), apoptosis (DAPI-sulforhodamine staining and caspase 3 activity) and IL-8 and VEGF secretion were determined. MXF or VP-16 slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of topo II. VP-16 induced cell cycle arrest at G2/M and the appearance of the subG1 peak which was increased by the addition of MXF. Apoptosis studies (DAPI staining and caspase 3 activity) showed a marked increase in the presence of MXF and VP-16 compared to VP-16 alone. VP-16 induced the release of IL-8, and addition of MXF reduced enhanced release and the spontaneous release of VEGF from the cells. In conclusion, the results suggest that the enhancement in the reduction of topo II activity by the combined MXF/VP-16 treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs. The unique combination of MXF/VP-16 may have clinical benefits and a cytotoxic drug 'sparing effect' and should be further studied in vivo.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_colon_rectum_cancers
Asunto principal:
Quinolinas
/
Compuestos Aza
/
Carcinoma
/
Apoptosis
/
Neoplasias del Colon
/
Etopósido
/
Inhibidores de Topoisomerasa II
Límite:
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2010
Tipo del documento:
Article
País de afiliación:
Israel