Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation

  • Authors:
    • Ann Huygens
    • Appolinary R. Kamuhabwa
    • An Van Laethem
    • Tania Roskams
    • Ben Van Cleynenbreugel
    • Hendrik Van Poppel
    • Patrizia Agostinis
    • Peter A.M. De Witte
  • View Affiliations

  • Published online on: June 1, 2005     https://doi.org/10.3892/ijo.26.6.1691
  • Pages: 1691-1697
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Abstract

The aim of this study was to explore the hypothesis of oxygen depletion during light irradiation as a possible explanation for the incomplete response seen after hypericin-mediated photodynamic therapy (PDT) under specific conditions. To investigate this, we performed PDT experiments using transitional cell carcinoma spheroids with fractionated light irradiation and hyperoxygenation. After 2-h incubation with 3 different hypericin concentrations, spheroids were irradiated either continuously or with fractionated light delivery. The effect of hyperoxygenation was investigated by bubbling normobaric oxygen in the solution surrounding the spheroids before continuous irradiation or during the dark interval of light fractionation. The PDT efficacy was evaluated with an MTT antiproliferation assay and apoptotic cells were visualized after PDT by DAPI staining. Our results show that fractionated light delivery with dark intervals ranging from 1 to 10 min does not enhance the PDT efficacy in spheroids at all, whereas hyperoxygenation, using appropriate hypericin concentrations and oxygenation intervals, results in a virtually complete malignant cell killing through apoptosis. This study suggests that oxygen depletion is the major source of relative treatment failure in hypericin-mediated PDT with spheroids, which can only be overcome with hyperoxygenation. Therefore, whole bladder wall PDT with hypericin is likely to become a very efficient antitumoural treatment against superficial bladder cancer, on the condition that instillation fluids are hyperoxygenated during light irradiation.

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June 2005
Volume 26 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Huygens A, Kamuhabwa AR, Van Laethem A, Roskams T, Van Cleynenbreugel B, Van Poppel H, Agostinis P and De Witte PA: Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation. Int J Oncol 26: 1691-1697, 2005
APA
Huygens, A., Kamuhabwa, A.R., Van Laethem, A., Roskams, T., Van Cleynenbreugel, B., Van Poppel, H. ... De Witte, P.A. (2005). Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation. International Journal of Oncology, 26, 1691-1697. https://doi.org/10.3892/ijo.26.6.1691
MLA
Huygens, A., Kamuhabwa, A. R., Van Laethem, A., Roskams, T., Van Cleynenbreugel, B., Van Poppel, H., Agostinis, P., De Witte, P. A."Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation". International Journal of Oncology 26.6 (2005): 1691-1697.
Chicago
Huygens, A., Kamuhabwa, A. R., Van Laethem, A., Roskams, T., Van Cleynenbreugel, B., Van Poppel, H., Agostinis, P., De Witte, P. A."Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation". International Journal of Oncology 26, no. 6 (2005): 1691-1697. https://doi.org/10.3892/ijo.26.6.1691