Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin-C in bladder cancer cells with different mechanisms

  • Authors: Matteo Ferro, Gaia Giuberti, Silvia Zappavigna, Sisto Perdonà, Gaetano Facchini, Pasquale Sperlongano, Stefania Porto, Giuseppe Di Lorenzo, Carlo Buonerba, Alberto Abbruzzese, Vincenzo Altieri, Michele Caraglia
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  • Published online on: Monday, October 31, 2011
  • Pages: 409-415
  • DOI: 10.3892/or.2011.1526

Abstract

Non-muscle invasive bladder cancer is the most common type of bladder cancer in Western countries. The glycosaminoglycan (GAG) layer at the bladder surface non-specifically blocks the adherence of bacteria, ions and molecules to the bladder epithelium and bladder cancer cells express CD44 that binds GAG. Currently, there are few options other than cystectomy for the management of non-muscle invasive bladder cancer with intravesical chemotherapy using several drugs such as gemcitabine (GEM) and mitomycin-C (MMC) with poor prophylactic activity. In this study, we investigated the effects of the GAG chondroitin sulphate (CS) on the growth inhibition of human bladder cancer cell lines HT-1376 and effects of the combination between GEM or MMC with CS. We have found that CS, MMC and GEM induced 50% growth inhibition at 72 h. Therefore, we have evaluated the growth inhibition induced by different concentration of CS in combination with MMC or GEM, respectively, at 72 h. We have observed, at Calcusyn analysis, a synergism when HT-1376 cells were treated with CS in combination with MMC or GEM, respectively, if used at an equimolar ratio. We have also found that CS/GEM combination induced a strong potentiation of apoptosis with the consequent activation of caspases 9 and 3. On the other hand, HT-1376 cells were necrotic if exposed to the CS/MMC combination and no signs of caspase activation was observed. In conclusion, in the human bladder cancer cell line HT-1376 pharmacological combination of CS with GEM or MMC resulted in a strong synergism on cell growth inhibition.
Journal Cover

February 2012
Volume 27 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.191
Ranked #33/202 Oncology
(total number of cites)

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APA
Ferro, M., Ferro, M., Giuberti, G., Giuberti, G., Zappavigna, S., Zappavigna, S., Perdonà, S., Perdonà, S., Facchini, G., Facchini, G., Sperlongano, P., Sperlongano, P., Porto, S., Porto, S., Di Lorenzo, G., Di Lorenzo, G., Buonerba, C., Buonerba, C., Abbruzzese, A., Abbruzzese, A., Altieri, V., Altieri, V., Caraglia, M., & Caraglia, M. (2012). Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin-C in bladder cancer cells with different mechanisms. Oncology Reports, 27(2), 409-415.
MLA
Ferro, Ferro, Giuberti, Giuberti, Zappavigna, Zappavigna, Perdonà, Perdonà, Facchini, Facchini, Sperlongano, Sperlongano, Porto, Porto, Di Lorenzo, Di Lorenzo, Buonerba, Buonerba, Abbruzzese, Abbruzzese, Altieri, Altieri, Caraglia, and Michele Caraglia. "Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin-C in bladder cancer cells with different mechanisms." Oncology Reports Oncology Reports 27.2 (2012): 409-415.
Chicago
Ferro, Ferro, Giuberti, Giuberti, Zappavigna, Zappavigna, Perdonà, Perdonà, Facchini, Facchini, Sperlongano, Sperlongano, Porto, Porto, Di Lorenzo, Di Lorenzo, Buonerba, Buonerba, Abbruzzese, Abbruzzese, Altieri, Altieri, Caraglia, and Michele Caraglia. "Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin-C in bladder cancer cells with different mechanisms." Oncology Reports Oncology Reports 27 no. 2 (2012): 409-415.