Related Experiment Video
Updated: Jun 8, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells
Emilia Peuhu1, Aura Kaunisto, Jarmo K Laihia
1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, BioCity, FI-20520 Turku, Finland.
Background:
cis-urocanic acid (cis-UCA) is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells.
Methods:
5367 bladder carcinoma cells were left untreated or treated with cis-UCA. Cell death was assessed by measuring caspase-3 activity, mitochondrial membrane polarization, formation and release of cytoplasmic histone-associated DNA fragments, and cellular permeabilization. Cell viability and metabolic activity were monitored by colorimetric assays. Nuclear labelling was used to quantify the effects of cis-UCA on cell cycle. The activity of the ERK and JNK signalling pathways was studied by immunoblotting with specific antibodies. Phosphatase activity in cis-UCA-treated cells was determined by assay kits measuring absorbance resulting from the dephosphorylation of an artificial substrate. All statistical analyses were performed using the two-way Student's t-test (p < 0.05).
Results:
Here we report that treatment of the 5637 human bladder carcinoma cells with 2% cis-UCA induces both apoptotic and necrotic cell death. In addition, metabolic activity of the 5637 cells is rapidly impaired, and the cells arrest in cell cycle in response to cis-UCA. Importantly, we show that cis-UCA promotes the ERK and JNK signalling pathways by efficiently inhibiting the activity of serine/threonine and tyrosine phosphatases.
Conclusions:
Our studies elucidate how cis-UCA modulates several cellular processes, thereby inhibiting the proliferation and survival of bladder carcinoma cells. These anti-cancer effects make cis-UCA a potential candidate for the treatment of non-muscle invasive bladder carcinoma.
Insights
cis-urocanic acid (cis-UCA) induces cancer cell death by acidifying the cytosol and inhibiting phosphatases, promoting cell cycle arrest. This suggests cis-UCA
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- cis-urocanic acid (cis-UCA) is an endogenous metabolite that transports protons, causing intracellular acidification and suppressing cellular functions.
- Understanding the molecular mechanisms of cis-UCA-induced cytotoxicity in cancer cells is crucial for therapeutic development.
Purpose of the Study:
- To investigate the molecular mechanisms underlying cis-urocanic acid (cis-UCA)-mediated cytotoxicity in cultured bladder carcinoma cells.
- To characterize the effects of cis-UCA on cell death, metabolism, cell cycle, and signaling pathways.
Main Methods:
- Treatment of 5637 bladder carcinoma cells with cis-UCA.
- Assessment of cell death via caspase-3 activity, mitochondrial membrane potential, and DNA fragmentation.
- Monitoring cell viability, metabolic activity, and cell cycle progression.
- Analysis of ERK and JNK signaling pathways and phosphatase activity.
Main Results:
- cis-UCA treatment induced both apoptotic and necrotic cell death in 5637 cells.
- Metabolic activity was impaired, and cells arrested in the cell cycle.
- cis-UCA promoted ERK and JNK signaling by inhibiting serine/threonine and tyrosine phosphatases.
Conclusions:
- cis-UCA effectively inhibits proliferation and survival of bladder carcinoma cells through modulation of cellular processes.
- cis-UCA demonstrates potential as a therapeutic agent for non-muscle invasive bladder carcinoma.
