Pseudomonas aeruginosa Exotoxin A Reduces Chemoresistance of Oral Squamous Carcinoma Cell via Inhibition of Heat Shock Proteins 70 (HSP70).
10.3349/ymj.2010.51.5.708
- Author:
Sang Rye PARK
1
;
Kyoung Duk LEE
;
Uk Kyu KIM
;
Young Gi GIL
;
Kyu Seon OH
;
Bong Soo PARK
;
Gyoo Cheon KIM
Author Information
1. Department of Oral Anatomy, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Korea. ki91000m@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Pseudomonas aeruginosa exotoxin A;
chemoresistance;
oral squamous cell carcinoma cells;
heat shock protein 70;
apoptosis
- MeSH:
ADP Ribose Transferases/*pharmacology;
Antineoplastic Agents/*pharmacology;
Apoptosis/drug effects;
Bacterial Toxins/*pharmacology;
Blotting, Western;
Carcinoma, Squamous Cell/drug therapy/*metabolism;
Cell Cycle/drug effects;
Cell Line, Tumor;
Chromatography, Liquid;
Cyclin B/metabolism;
Cyclin-Dependent Kinase 2/metabolism;
Drug Resistance, Neoplasm/*drug effects;
E2F1 Transcription Factor/metabolism;
Electrophoresis;
Exotoxins/*pharmacology;
HSP70 Heat-Shock Proteins/genetics/*metabolism;
Humans;
In Situ Nick-End Labeling;
Mouth Neoplasms/drug therapy/*metabolism;
Tandem Mass Spectrometry;
Tumor Suppressor Protein p53/metabolism;
Virulence Factors/*pharmacology
- From:Yonsei Medical Journal
2010;51(5):708-716
- CountryRepublic of Korea
- Language:English
-
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 AND METHODS: 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.
