Photodynamic action of meta-tetrahydroxyphenylchlorin (mTHPC) on an ovarian cancer cell line.
Meta-tetrahydroxyphenylchlorin (mTHPC) exhibits significant cytotoxicity against a variety of human cells in culture in combination with light, but also in dark reaction. The ovarian cancer cell line SK-OV3 was incubated with various concentrations of mTHPC and in comparison with Taxol and Cisplatin: then the effect on cell growth was determined. mTHPC exhibited an IC50 of 0.9 muM after 24 hours incubation (IC50 of 1.25 after 2 hours), whereas Cisplatin and Taxol, which, have been used as first line agents for the treatment of ovarian carcinomas, inhibited cell proliferation with an IC50 concentration of 4.6 muM and 78 nM after 24 hours incubation, respectively. Incubation of SK-OV3 cells with mTHPC for 5 days resulted in cytostatic cytotoxicity at a concentration of 0.5 muM. The photodynamic effect of mTHPC depends/among other parameters/on the concentration of the dye present. In combination with light (approximately 15 J/cm2) a linear relationship between the dose of mTHPC and the amount of necrotic cells was observable. Higher concentrations of mTHPC caused necrosis of the ovarian tumor cells. The intracellular concentration of mTHPC showed a linear increase up to 28.6 nM (incubation concentration). In summary, these studies demonstrated that mTHPC exhibits potent antiproliferative activity by inducing necrosis after application of light. MTHPC might be a promising agent with cytostatic and photodynamic properties for the treatment of metastasing ovarian carcinomas. A sensitive PCR method was not able to show the induction of apoptosis in the SK-OV3 ovarian cell line. Using propidium staining, it could be proved that the cell death was caused by necrosis and not through apoptosis after irradiation with light.
Gharehbaghi
K
K
Department of Obstetrics and Gynecology, Rudolfsuftung Hospital, Vienna, Austria.
Kubin
A
A
Grusch
M
M
Gharehbaghi-Schnell
E
E
Wierrani
F
F
Jayaram
H N
HN
Grunberger
W
W
Szekeres
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D006801:Humans; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D009336:Necrosis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; C072269:temoporfin; D017239:Paclitaxel; D002945:Cisplatin