Hypericin and 5-aminolevulinic acid-induced protoporphyrin IX induce enhanced phototoxicity in human endometrial cancer cells with non-coherent white light

Schneider-Yin, Xiaoye; Kurmanaviciene, Aida; Roth, Marion; Roos, Malgorzata; Fedier, André; Minder, Elisabeth I.; Walt, Heinrich

doi:10.1016/j.pdpdt.2009.02.001

« Previous Next »Photodiagnosis and Photodynamic Therapy
Volume 6, Issue 1 , Pages 12-18, March 2009

Hypericin and 5-aminolevulinic acid-induced protoporphyrin IX induce enhanced phototoxicity in human endometrial cancer cells with non-coherent white light

Xiaoye Schneider-Yin, PhD
- Central Laboratory, Triemli Hospital, Zurich, Switzerland
- Corresponding author at: Central Laboratory, Triemli Hospital, Birmensdorferstr. 497, CH-8063 Zurich, Switzerland. Tel.: +41 44 466 23 35; fax: +41 44 466 27 09.
Aida Kurmanaviciene
- Research Division, Department of Gynecology, University Hospital, Switzerland
Marion Roth
- Central Laboratory, Triemli Hospital, Zurich, Switzerland
Malgorzata Roos
- Biostatistics Unit, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland
André Fedier
- Research Division, Department of Gynecology, University Hospital, Switzerland
Elisabeth I. Minder
- Central Laboratory, Triemli Hospital, Zurich, Switzerland
Heinrich Walt
- Research Division, Department of Gynecology, University Hospital, Switzerland

published online 16 March 2009.

Summary

Background

The in vitro experiments described in this study were aimed at exploring a synergistic effect between 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) and hypericin. In a previous study, enhanced phototoxicity was observed in a patient during a clinical study on 5-ALA-based photodynamic tumor localization of breast cancer. This patient ingested a hypericin containing plant extract in parallel to orally applied 5-ALA.

Methods

Human endometrial cancer cells (HEC-1A) were treated with 0.5mM of 5-ALA and 60nM of hypericin, either separately or combined. Colony formation was assessed after illumination of the cells with both red (635nm) and white light (400–800nm) at a dose of 2.5J/cm². Porphyrin metabolites were quantified by HPLC in cells treated with photosensitizers without subsequent illumination.

Results

After white light illumination, cells treated with a combination of 5-ALA and hypericin had a significant reduction in colony formation compared with cells treated with 5-ALA only. No significantly enhanced toxicity was found with red light and the 5-ALA plus hypericin combination. In addition, cells treated with both 5-ALA and hypericin tended to produce more PpIX than cells treated with 5-ALA only.

Conclusions

This study demonstrated that treatment of endometrial cancer cells with both 5-ALA and hypericin followed by illumination with white light induced a significantly higher phototoxicity as revealed by colony formation. This setting which generated an in vitro effect similar to the patient's situation, might be applied in the future as an affordable and effective photodynamic therapy (PDT) modality.

Abbreviations: 5-ALA, 5-aminolevulinic acid, PpIX, protoporphyrin IX, PDT, photodynamic therapy, PDD, photodynamic detection, HEC-1A, human endometrial cancer cells-1A, HPLC, high performance liquid chromatography