K. Gharehbaghi et al., Photodynamic action of meta-tetrahydroxyphenylchlorin (mTHPC) on an ovarian cancer cell line, ANTICANC R, 20(4), 2000, pp. 2647-2652
Meta-tetrahydroxyphenylchlorin (mTHPC) exhibits significant cytotoxicity ag
ainst a variety of human cells in culture in combination with light, but al
so 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 mu M after 24 hours incubation (IC50 of 1.25 after 2 hours), whereas C
isplatin and Taxol, which, have been used as first line agents for the trea
tment of ovarian carcinomas, inhibited cell proliferation with an IC50 conc
entration of 4.6 mu M and 78 nM after 24 hours incubation, respectively. In
cubation of SK-OV3 cells with mTHPC for 5 days resulted in cytostatic cytot
oxicity ata concentration of 0.5 mu M. The photodynamic effect of mTHPC dep
ends/among other parameters/on the concentration of the dye present. In com
bination with light (approximate to 15 J/cm(2)) a linear relationship betwe
en the dose of mTHPC and the amount of necrotic cells was observable. Highe
r concentrations of mTHPC caused necrosis of the ovarian tumor cells. The i
ntracellular concentration of mTHPC showed a linear increase up to 28.6 nM
(incubation concentration). In summary, these studies demonstrated that mTH
PC exhibits potent antiproliferative activity by inducing necrosis after ap
plication of Eight. MTHPC might be a promising agent with cytostatic and ph
otodynamic properties for the treatment of metastising ovarian carcinomas.
A sensitive PCR method was not able to show the induction of apoptosis in t
he SK-OV3 ovarian cell line. Using propidium staining, it could be proved t
hat the cell death was caused by necrosis and not through apoptosis after i
rradiation with light.