Pseudomonas aeruginosa Exotoxin A Reduces Chemoresistance of Oral Squamous Carcinoma Cell via Inhibition of Heat Shock Proteins 70 (HSP70)
Yonsei Medical Journal
;
: 708-716, 2010.
Artículo
en Inglés
| WPRIM
| ID: wpr-53355
ABSTRACT
PURPOSE:
Oral squamous carcinoma (OSCC) cells exhibit resistance to chemotherapeutic agent-mediated apoptosis in the late stage of malignancy. Increased levels of heat shock proteins 70 (HSP70) in cancer cells are known to confer resistance to apoptosis. Since recent advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers, we investigated the effect of Pseudomonas aeruginosa exotoxin A (PEA) on HSP70 expression and induction of apoptosis in chemoresistant OSCC cell line (YD-9). MATERIALS ANDMETHODS:
The apoptotic effect of PEA on chemoresistant YD-9 cells was confirmed by MTT, Hoechst and TUNEL stains, DNA electrophoresis, and Western blot analysis.RESULTS:
While YD-9 cells showed high resistance to chemotherapeutic agents such as etoposide and 5-fluorouraci (5-FU), HSP70 antisense oligonucelotides sensitized chemoresistant YD-9 cells to etoposide and 5-FU. On the other hand, PEA significantly decreased the viability of YD-9 cells by deteriorating the HSP70-relating protecting system through inhibition of HSP70 expression and inducing apoptosis in YD-9 cells. Apoptotic manifestations were evidenced by changes in nuclear morphology, generation of DNA fragmentation, and activation of caspases. While p53, p21, and E2F-1 were upregulated, cdk2 and cyclin B were downregulated by PEA treatment, suggesting that PEA caused cell cycle arrest at the G2/M checkpoint.CONCLUSION:
Therefore, these results indicate that PEA reduced the chemoresistance through inhibition of HSP70 expression and also induced apoptosis in chemoresistant YD-9 cells.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Toxinas Bacterianas
/
Neoplasias de la Boca
/
Carcinoma de Células Escamosas
/
Ciclo Celular
/
Western Blotting
/
Cromatografía Liquida
/
Proteína p53 Supresora de Tumor
/
ADP Ribosa Transferasas
/
Apoptosis
/
Proteínas HSP70 de Choque Térmico
Límite:
Humanos
Idioma:
Inglés
Revista:
Yonsei Medical Journal
Año:
2010
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS