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Protodynamic therapy for bladder cancer: in vitro results of a novel treatment concept
Author(s) -
Laihia Jarmo K.,
Pylkkänen Liisa,
Laato Matti,
Boström Peter J.,
Leino Lasse
Publication year - 2009
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2009.08611.x
Subject(s) - epirubicin , bladder cancer , cisplatin , doxorubicin , paclitaxel , cell growth , cell culture , cancer cell , chemistry , pharmacology , viability assay , cancer research , cell , in vitro , cytotoxic t cell , cancer , chemotherapy , biology , medicine , biochemistry , cyclophosphamide , genetics
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 ≤ 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.