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.

PubMed

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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