Photodynamic therapy with hypericin in a mouse P388 tumor model

vascular effects determine the efficacy.

B. Chen, I. Zupkó, P. A. de Witte

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Hypericin, a polycyclic quinone obtained from plants of the Hypericum genus, exhibits strong photodynamic antitumor effects. In the present study, PDT efficacy of hypericin under different conditions was compared in a P388 mouse tumor model. Plasma and tumor drug measurements and assessment of vascular damage by fluorescein dye exclusion were performed to determine the relative contributions of vascular effects and direct tumor cytotoxicity. Furthermore, the influence of modifying tumor oxygenation on PDT effect was also evaluated. Study of PDT efficacy and tissue distribution revealed that PDT efficacy was more dependent on plasma concentration than tumor drug level. Fluorescein dye exclusion indicated the complete microvascular occlusion in the tumor and surrounding skin immediately after effective PDT treatments, while only a limited vascular occulation was observed after non-effective PDT treatment. It was found that neither tumor hypoxia induced by hydralazine nor increasing tumor oxygenation achieved by nicotinamide could significantly affect the effectiveness of various PDT protocols. These results suggest that tumor vasculature damage might be the primary mechanism of hypericin-mediated PDT effect. The existence of this potent secondary vascular effect is likely to account for the inability of tumor oxygenation modifiers to affect tumor response after PDT with hypericin.

Original languageEnglish
Pages (from-to)737-742
Number of pages6
JournalInternational Journal of Oncology
Volume18
Issue number4
Publication statusPublished - Apr 2001

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Photochemotherapy
Blood Vessels
Neoplasms
Fluorescein
Coloring Agents
hypericin
Hypericum
1-phenyl-3,3-dimethyltriazene
Hydralazine
Niacinamide
Tissue Distribution
Pharmaceutical Preparations
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Photodynamic therapy with hypericin in a mouse P388 tumor model : vascular effects determine the efficacy. / Chen, B.; Zupkó, I.; de Witte, P. A.

In: International Journal of Oncology, Vol. 18, No. 4, 04.2001, p. 737-742.

Research output: Contribution to journalArticle

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