Curcumin combined with exposure to visible light blocks bladder cancer cell adhesion and migration by an integrin dependent mechanism

J. Mani, J. Fleger, J. Rutz, S. Maxeiner, A. Bernd, S. Kippenberger, N. Zöller, F.K.-H. Chun, B. Relja, E. Juengel, R.A. Blaheta

Department of Urology, Goethe-University, Frankfurt am Main, Germany. blaheta@em.uni-frankfurt.de

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• Pharmacology

OBJECTIVE: Although the natural compound curcumin exerts antitumor properties in vitro, its clinical application is hampered due to rapid metabolism. Light exposure following curcumin application has been demonstrated to improve curcumin’s bioavailability. Therefore, this investigation was directed towards evaluating whether light exposure in addition to curcumin application enhances curcumin’s efficacy against bladder cancer cell adhesion and migration.

MATERIALS AND METHODS: RT112, UMUC3, and TCCSUP cells were incubated with low curcumin concentrations (0.1-0.4 μg/ml) and then exposed to 1.65 J/cm2 visible light for 5 min. Controls remained untreated or were treated with curcumin or light alone. Cell adhesion to Human umbilical vein endothelial cells (HUVECs), to immobilized collagen or fibronectin and chemotactic behavior, integrin α and β receptor expression with functional relevance, as well as focal adhesion kinase (total and phosphorylated FAK) were evaluated.

RESULTS: Curcumin plus light, but neither curcumin nor light alone, significantly altered tumor cell adhesion and suppressed chemotaxis. Integrin α and β subtypes were dissimilarly modified, depending on the cell line. Suppression of pFAK was noted in RT112 and UMUC3, but not in TCCSUP cells. The integrins α3, α5, and β1 were involved in curcumin’s regulation of adhesion and migration. Blocking studies revealed α3, α5, and β1 to be associated with TCCSUP adhesion and migration, whereas α5 and β1, but not α3 contributed to UMUC3 adhesion and migration. Integrin α5 and β1 controlled RT112 chemotaxis as well, but only α5 was involved in the RT112 adhesion process.

CONCLUSIONS: Combining curcumin with light exposure enhances curcumin’s anti-tumor potential.

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