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Updated: Feb 14, 2026

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Natural Isothiocyanates Block Adhesion and Invasion of Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines
Jochen Rutz1, Timothy Grein1,2, Marina Laqua2
1Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany.
Abstract:
Aggressive metastatic progression often develops in bladder cancer patients with acquired cisplatin or gemcitabine resistance. The potential of the natural isothiocyanates allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to inhibit adhesion and migration of cisplatin- or gemcitabine-resistant and sensitive RT112, T24, and TCCSUP bladder cancer cell lines was investigated. Parameters determined were: cell interaction with collagen or fibronectin, chemotaxis, and membrane receptors involved in adhesion (total and activated integrins β1, β4, β5, CD44s, and CD44v3-v7). CD44s' location and adhesion- and migration-related signaling proteins were determined. AITC blocked adhesion of almost all sensitive and resistant cancer cells. PEITC and BITC suppressed fibronectin interaction of sensitive and resistant RT112. All three isothiocyanates diminished chemotaxis in all cell lines. Integrin expression was differentially altered but CD44s and CD44v were not altered. BITC and PEITC translocated CD44s from the cell membrane to cytoplasm. The tumor suppressor E-cadherin increased, whereas focal adhesion kinase (FAK), linked to integrin signaling, was deactivated after isothiocyanate treatment. Blocking FAK, β1, β4, or β5 was associated with reduced chemotaxis. Thus, AITC, BITC, and PEITC blocked adhesion and migration in cisplatin- and gemcitabine-resistant bladder cancer cells. This was associated with altered integrin expression and signaling, CD44s translocation, and enhanced E-cadherin.
Insights
Natural isothiocyanates like allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) effectively inhibited bladder cancer cell adhesion and migration, even in drug-resistant cells. These compounds offer potential for new bladder cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Bladder cancer often progresses aggressively, particularly with resistance to cisplatin or gemcitabine.
- Acquired resistance to chemotherapy significantly complicates treatment strategies for bladder cancer patients.
Purpose of the Study:
- To investigate the potential of natural isothiocyanates (AITC, BITC, PEITC) in inhibiting bladder cancer cell adhesion and migration.
- To evaluate the efficacy of these compounds against both sensitive and drug-resistant bladder cancer cell lines.
- To elucidate the molecular mechanisms underlying the anti-adhesion and anti-migration effects.
Main Methods:
- Assessed cell adhesion to collagen and fibronectin.
- Measured chemotaxis and analyzed membrane receptors (integrins, CD44s, CD44v).
- Determined CD44s localization and signaling proteins, including focal adhesion kinase (FAK) and E-cadherin.
Main Results:
- AITC blocked adhesion in most sensitive and resistant bladder cancer cells.
- PEITC and BITC inhibited fibronectin interaction in RT112 cells.
- All isothiocyanates reduced cell chemotaxis.
- Isothiocyanates altered integrin expression, translocated CD44s, increased E-cadherin, and deactivated FAK.
- Blocking FAK and specific integrins reduced chemotaxis.
Conclusions:
- Allyl-isothiocyanate, BITC, and PEITC effectively inhibit adhesion and migration in cisplatin- and gemcitabine-resistant bladder cancer cells.
- These effects are linked to altered integrin signaling, CD44s translocation, and increased E-cadherin expression.
- Isothiocyanates show promise as therapeutic agents against aggressive and resistant bladder cancer.
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