Protodynamic therapy for bladder cancer: in vitro results of a novel treatment concept.

Abstract

OBJECTIVE:

To present a novel treatment approach for urinary bladder cancer, protodynamic therapy, which comprises inhibition of cancer cell proliferation by intracellular acidification; cis-urocanic acid (cis-UCA) was investigated as a protodynamic drug in bladder cancer cell cultures and compared with conventional chemotherapeutic agents.

MATERIALS AND METHODS:

The moderately differentiated cell line 5637 and the poorly differentiated T24 cell line were exposed to cis-UCA for 0.25-2 h, and to epirubicin, doxorubicin, cisplatin and paclitaxel for 2 h, to simulate drug exposure on intravesical instillation. The combination of cis-UCA and chemotherapeutic agents was also studied. Cell viability was measured with a colorimetric assay.

RESULTS:

cis-UCA inhibited proliferation and suppressed the survival of cells at an extracellular pH <or= pK(a2) of 6.65 but to a lesser degree at pH > pK(a2), as suggested by the protodynamic theory. cis-UCA caused dose-dependent, irreversible termination of cell proliferation. The number of viable surviving BC cells decreased by >85% with 2%cis-UCA (P < 0.001). Viable cells disappeared completely with 4% and 6%cis-UCA after a 2-h treatment, and by 90% with 6%cis-UCA within a 15-min exposure. These effects were associated with distinct morphological changes. The other drugs tested had a clearly lower effect on cell survival. Interestingly, when combined, cis-UCA markedly enhanced the cytotoxic effect of epirubicin.

CONCLUSION:

cis-UCA is a potent antiproliferative agent in bladder cancer cell cultures. As our previous non-clinical studies showed that cis-UCA is locally and systemically well tolerated, protodynamic therapy with cis-UCA is a promising intravesical treatment for bladder cancer.

• Authors: Jarmo K Laihia, Liisa Pylkkänen, Matti Laato, Peter J Boström, Lasse Leino
• Journal: BJU international (BJU Int) Vol. 104 Issue 9 Pg. 1233-8 (Nov 2009) ISSN: 1464-410X [Electronic] England
• PMID: 19466948 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epirubicin
• Doxorubicin
• Urocanic Acid
• Paclitaxel
• Cisplatin

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Transitional Cell (drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cisplatin (administration & dosage)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage)
• Drug Synergism
• Epirubicin (administration & dosage)
• Humans
• Hydrogen-Ion Concentration
• Paclitaxel (administration & dosage)
• Photochemotherapy (methods)
• Urinary Bladder Neoplasms (drug therapy)
• Urocanic Acid (administration & dosage)