Hypericin-mediated photodynamic therapy of pituitary tumors: preclinical study in a GH4C1 rat tumor model

J Neurooncol. 2008 May;87(3):255-61. doi: 10.1007/s11060-007-9514-0. Epub 2008 Jan 29.

Abstract

Objective: Hypericin-mediated photodynamic therapy (PDT) is receiving greater interest as a potential treatment for a variety of tumors and nonmalignant disorders. PDT involves systemic administration of a photosensitizer that selectively accumulates within tumor tissue followed by focal light activation. In the presence of molecular oxygen, a photochemical reaction generates a reactive oxygen species that induces apoptosis in target cells. The purpose of this preclinical study was to evaluate the efficacy of hypericin-mediated PDT for treatment of pituitary adenoma in a rodent model.

Methods: Wistar-Furth rats were implanted with a pituitary adenoma rat cell line, GH4C1. Tumor masses were allowed to develop over 28 days; rats with tumors of comparable sizes were then assigned to three treatment groups: control (neither hypericin nor light); light only; and hypericin and light. Hypericin was administered in four doses (1 mg/kg) at 28-h intervals prior to light exposure, wherein those rats treated with light were exposed to a light source four hours after the last hypericin dose. Tumor size was measured up to 12 days after treatment.

Results: Over the short interval examined, hypericin-mediated PDT was not effective against large tumors greater than 1 cm(3), but this treatment significantly slowed tumor growth for tumors less than 1 cm(3). Histological evaluation and TUNEL assay of the treated tumor identified apoptotic clusters on the periphery of the PDT-treated specimens.

Conclusions: Hypericin-mediated PDT shows promise in its effectiveness in the treatment of residual small tumor rests.

MeSH terms

  • Animals
  • Anthracenes
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • In Situ Nick-End Labeling
  • Perylene / analogs & derivatives*
  • Perylene / therapeutic use
  • Photochemotherapy*
  • Pituitary Neoplasms / drug therapy*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Rats
  • Rats, Wistar

Substances

  • Anthracenes
  • Radiation-Sensitizing Agents
  • Perylene
  • hypericin