Photosensitizing and radiosensitizing effects of hypericin on human renal carcinoma cells in vitro.
The renal cell carcinoma (RCC) is extremely resistant to chemotherapy and radiotherapy. The prognosis of patients with metastatic RCC still remains poor, the median survival is less than 12 months. Therefore, new therapeutic options are desirable. The aim of this study was to investigate the photosensitizing and radiosensitizing effects of hypericin on human RCC cells in vitro. First the RCC-derived cell lines A498 and ACHN were incubated with different concentrations of hypericin. In vitro uptake and intracellular distribution of hypericin were confirmed by fluorescence microscopy. Subsequently cells were illuminated and irradiated with a dose of 2-8 Gy, respectively. Finally, metabolic activity, apoptosis and clonogenic survival were investigated. Uptake of hypericin was observed for almost all cells. Hypericin treatment combined with illumination led to a 94-97% decrease in metabolic activity and caused apoptosis in nearly 100% of RCC cells. Hypericin enhanced the radiosensitivity of A498 cells in vitro. The clonogenic survival after irradiation was significantly reduced by hypericin treatment. Taken together, the photosensitizing and radiosensitizing effects of hypericin on human RCC cells we found in this investigation could be of clinical relevance, e.g. for radiotherapy and intraoperative photodynamic therapy, respectively.
Wessels
Johannes Theodor
JT
Center of Internal Medicine, Department of Nephrology/Rheumatology, University Hospital, Göttingen, Germany. johannes.wessels@med.uni-goettingen.de
Busse
Ann-Christin
AC
Rave-Fränk
Margret
M
Zänker
Stephan
S
Hermann
Robert
R
Grabbe
Eckhardt
E
Müller
Gerhard-Anton
GA
D000873:Anthracenes; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*
D000873:Anthracenes; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin