Pseudomonas aeruginosa Exotoxin A Reduces Chemoresistance of Oral Squamous Carcinoma Cell via Inhibition of Heat Shock Proteins 70 (HSP70)

• Published in: Yonsei medical journal Vol. 51; no. 5; pp. 708 - 716
• Main Authors: Park, Sang Rye, Lee, Kyoung Duk, Kim, Uk Kyu, Gil, Young Gi, Oh, Kyu Seon, Park, Bong Soo, Kim, Gyoo Cheon
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.09.2010; 연세대학교의과대학
• Subjects: ADP Ribose Transferases - pharmacology; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Bacterial Toxins - pharmacology; Blotting, Western; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - 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; HSP70 Heat-Shock Proteins - metabolism; Humans; In Situ Nick-End Labeling; Mouth Neoplasms - drug therapy; Mouth Neoplasms - metabolism; Original; Pseudomonas aeruginosa Exotoxin A; Tandem Mass Spectrometry; Tumor Suppressor Protein p53 - metabolism; Virulence Factors - pharmacology; 의학일반
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2010.51.5.708

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). The apoptotic effect of PEA on chemoresistant YD-9 cells was confirmed by MTT, Hoechst and TUNEL stains, DNA electrophoresis, and Western blot analysis. 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. Therefore, these results indicate that PEA reduced the chemoresistance through inhibition of HSP70 expression and also induced apoptosis in chemoresistant YD-9 cells.