Permeation of hypericin in spheroids composed of different grade transitional cell carcinoma cell lines and normal human urothelial cells |
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Authors: | Huygens Ann Kamuhabwa Appolinary R Roskams Tania VAN Cleynenbreugel Ben VAN Poppel Hendrik de Witte Peter A M |
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Institution: | Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium. |
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Abstract: | PURPOSE: We investigated the importance of E-cadherin expression on the selective accumulation of hypericin in superficial bladder cancer after intravesical instillation. MATERIALS AND METHODS: Spheroids obtained from a panel of 3 transitional cell carcinoma cell lines, namely J-82, RT-4 (American Type Culture Collection, Manassas, Virginia) and RT-112 (German Collection of Micro-organisms and Cell Cultures, Braunschweig, Germany), and normal human urothelial (NHU) cells were incubated with hypericin. Accumulation was examined with fluorescence microscopy. Immunohistochemical staining was used to assess E-cadherin expression. RESULTS: Immunohistochemical staining showed E-cadherin expression in NHU (++), RT-112 (+) and RT-4 (+) spheroids, whereas E-cadherin expression was absent in J-82 spheroids. The highest intraspheroidal hypericin accumulation was observed in transitional cell carcinoma spheroids, whereas limited permeation was seen in NHU spheroids. Taken together the data point to an inverse relationship between E-cadherin expression and the permeation of hypericin throughout a 3-dimensional cellular matrix. CONCLUSIONS: Loss of E-cadherin expression correlates with loss of intercellular adhesion, tight junction formation and enhanced paracellular transport. The data show that E-cadherin hampers the permeation of hypericin in spheroids and the loss of intercellular adhesion, present in superficial bladder cancer lesions, can be associated with enhanced hypericin permeation. Therefore, E-cadherin expression seems to have a pivotal role in the selective uptake of hypericin after intravesical instillation in human bladders. |
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Keywords: | Key Words:: bladder neoplasms hypericin cadherins bladder spheroids cellular |
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