Hypericin-mediated photodynamic therapy of pituitary tumors: preclinical study in a GH4C1 rat tumor model.
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.
Cole
Chad D
CD
Department of Neurosurgery, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA.
Liu
James K
JK
Sheng
Xiaoming
X
Chin
Steven S
SS
Schmidt
Meic H
MH
Weiss
Martin H
MH
Couldwell
William T
WT
D000818:Animals; D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020287:In Situ Nick-End Labeling; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy; D010911:Pituitary Neoplasms / Q000188:drug therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin