Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Cytostatic in vitro Effects of DTCM-Glutarimide on Bladder Carcinoma Cells

  • Brassesco, Maria S. (Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • Pezuk, Julia A. (Department of Genetics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • Morales, Andressa G. (Department of Genetics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • De Oliveira, Jaqueline C. (Department of Genetics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • Valera, Elvis T. (Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • Da Silva, Glenda N. (Faculty of Medicine of Botucatu, Sao Paulo State University - UNESP) ;
  • De Oliveira, Harley F. (Division of Radiotherapy, Clinics Department, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • Scrideli, Carlos A. (Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP) ;
  • Umezawa, Kazuo (Faculty of Science and Technology, Keio University) ;
  • Tone, Luiz G. (Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo - USP)
  • Published : 2012.05.30
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Abstract

Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 ${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

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References

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