Assessment of effect of photosensitizers on cytotoxicity of photodynamic therapy in human breast cancer cell cultures.
BACKGROUND
Photodynamic therapy (PDT) might be of clinical value for patients with breast cancer with local recurrences or metastasis. However, there is a need for improved photosensitizers that are effective in combination with laser light and have few, if any, side-effects. We evaluated in vitro the effectiveness of a second generation photosensitizer by testing the influence of laser light on cell cultures of a human breast carcinoma cell line, incubated with meta-tetrahydroxyphenylchlorin (m-THPC) (= Temoporfin).


METHODS
Five thousand MCF-7 cells were plated in 96-well plates. Forty-eight hours before laser treatment, the cells were plated to achieve a monolayer configuration. Twenty-four hours after plating, they were incubated with m-THPC. On day 6 after treatment with m-THPC we lysed the cells to extract the intracellular ATP that correlates with the number of living cells. The ATP-CVA was used to assess the cytotoxicity of the tested photosensitizer m-THPC at various concentrations and the relevant laser light alone prior to their combination after six days of culture.


RESULTS
We found a dose-response for m-THPC alone ranging from 2 to 16 micrograms/ml. The calculated inhibition concentration to produce 50% cell kill (IC50) was 4.55 micrograms/ml. We also observed a very low cytotoxicity for laser irradiation alone but a very strong cell kill for the combination of m-THPC together with laser light.


CONCLUSIONS
PDT gave almost total cell kill at m-THPC concentrations that are not toxic in vitro.
Koechli
O R
OR
Department of Obstetrics & Gynecology, University of Zürich, Switzerland.
Schaer
G N
GN
Schenk
V
V
Haller
U
U
Walt
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008652:Mesoporphyrins / Q000494:pharmacology*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; D000255:Adenosine Triphosphate; C072269:temoporfin