Advertisement

Synthetic Smac peptide enhances chemo-sensitivity of bladder cancer cells

  • Jing Wang (王 竞)
  • Fuqing Zeng (曾甫清)
  • Liang Wang (汪 良)
  • Zhaohui Zhu (朱朝辉)
  • Guosong Jiang (蒋国松)
Article

Summary

The effects of synthetic Smac peptide (SmacN7) on chemotherapeutic sensitivity of bladder cancer cells were investigated. SmacN7 penetratin peptide was synthesized and delivered into T24 cells. MTT assay was used to evaluate the viability of T24 cells induced by low-dosage of MMC. Flow cytometry was used to analyze the proportions of apoptosis. Western blot was used to detect the expression of XIAP and Caspase-3. The activity of Caspase-3 was measured and the effect of SmacN7 combined with MMC on T24 cell lines was also determined. The results showed that SmacN7 penetratin peptide could successfully interact with endogenous XIAP, increase the proportions of apoptosis of T24 cell lines induced by low-dosage of MMC in a dose-and time-dependent manner. An obvious down-regulation of XIAP expression and up-regulation of Caspase-3 was identified by Western blot. The activity of Caspase-3 in experimental group was significantly increased as compared with that in the control group. As compared with MMC group, the viability of T24 cells in SmacN7 penetratin peptide+MMC group was markedly decreased to 2.22 and 3.61 folds at 24 h and 48 h respectively. It was concluded that SmacN7 penetratin peptide could act as a cell-permeable IAP inhibitor, inhibit the proliferation, induce apoptosis and enhance the chemo-sensitivity of bladder cancer cells to MMC. These findings indicate that SmacN7 penetratin peptide may be a very promising ageut for bladder cancer treatment when used in combination with chemotherapy.

Key words

Smac/DIABLO synthetic peptide bladder carcinoma chemo-sensitivity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hasenjager A, Gillisen B, Muller A et al. Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-xl in a strictly Caspase-3-dependent manner in human carcinoma cells. Oncogene, 2004,23(26):4523–4535PubMedCrossRefGoogle Scholar
  2. 2.
    Hickman J A. Apoptosis induced by anticancer drugs. Cancer Metestasis Rev, 1992,11:121–139CrossRefGoogle Scholar
  3. 3.
    Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell, 2002,9:459–470PubMedCrossRefGoogle Scholar
  4. 4.
    Vucic D, Deshayes K, Ackerly H et al. SMAC negatively regulates the anti-apoptotic activity of melanoma of apoptosis (ML-IAP). J Biol Chem, 2002, 277:12 275–12 279CrossRefGoogle Scholar
  5. 5.
    Liu Z, Sun C, Olejniczak E T et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature, 2000,408(6815):1004–1008PubMedCrossRefGoogle Scholar
  6. 6.
    Korga A, Korobowicz E, Dudka J. Role of mitochondrial protein Smac/Diablo in regulation of apoptotic pathways. Pol Merkur Lekarski, 2006,20(119):573–576PubMedGoogle Scholar
  7. 7.
    Chauhan D, Neri P, Velankar M et al. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Blood, 2007,109(3):1220–1227PubMedCrossRefGoogle Scholar
  8. 8.
    Glover C J, Hite K, DeLosh R. A high-throughout screen for identification of molecular mimics of Smac/DIABLO utilizing a fluorescence polarization assay. Analytic Biochemistry, 2003,320:157–169CrossRefGoogle Scholar
  9. 9.
    Fulda S, Wick W, Weller M et al. Smac agonists sensitize for Apo2L/TRAIL-or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med, 2002,8:808–815PubMedGoogle Scholar
  10. 10.
    Yang L, Mashima T, Sato S et al. Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res, 2003,63(4):831–837PubMedGoogle Scholar
  11. 11.
    Thoren P E, Persson D, Karlsson M et al. The antennapedia peptide penetration translocates across lipid bilayers — the first direct observation. FEBS Lett, 2000,482(3):265–268PubMedCrossRefGoogle Scholar
  12. 12.
    Mizukawa K, Kawamura A, Sasayama T et al. Synthetic Smac peptide enhances the effect of etoposide-induced apoptosis in human glioblastoma cell lines. J Neurooncol, 2006,77(3):247–255PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag GmbH 2008

Authors and Affiliations

  • Jing Wang (王 竞)
    • 1
  • Fuqing Zeng (曾甫清)
    • 1
  • Liang Wang (汪 良)
    • 1
  • Zhaohui Zhu (朱朝辉)
    • 1
  • Guosong Jiang (蒋国松)
    • 1
  1. 1.Department of UrologyUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina

Personalised recommendations