Influence of temperature on the efficiency of photodestruction of Ehrlich ascites carcinoma cells sensitized by hematoporphyrin derivative.
OBJECTIVE
To elucidate the mechanism of the potentiating influence of heating associated with photoirradiation on the antitumor efficiency of photodynamic therapy (PDT) with hematoporphyrin derivative (HPD).


METHODS
The study was carried out on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in a serum-free medium and then irradiated with red light (lambda max=630 nm) at various temperatures. Cytotoxicity was estimated by the trypan blue exclusion assay.


RESULTS
Our data support the view that in PDT the hyperthermia (around 44 degrees C) produced by irradiation can enhance synergistically the HPD-photoinduced tumor eradication; it was found that raising the irradiation temperature from 30 to 44 degrees C caused a substantial (approximately 1.5 fold) increase in the rate of HPD-photosensitized inactivation of EAC cells, while hyperthermia (44 degrees C) itself showed little toxic effects towards the cells.


CONCLUSIONS
Studies indicated that the potentiating effect of heating on the antitumor efficiency of HPD-PDT could be largely explained by the stimulation of reactive oxygen species formation such as H2O2, superoxide and hydroxyl radicals. It was also found that photosensitization of EAC cells by HPD caused a strong fall in the activity of catalase (CAT) and glutathione (GSH) peroxidase, and that heating sensitized the H2O2-detoxifying enzymes to HPD-photoinduced inactivation. Under HPD-PDT, these events could result in loss of protection against accumulating H2O2; we revealed that cell-bound CAT and the GSH redox cycle play an important role in the protection of EAC cells against HPD-PDT. Moreover, our findings suggest that during PDT with HPD, an increase in the temperature of tumors could enhance the efficiency of this therapy via the stimulation of a chlorin-type photoproduct formation.
Department of Chemistry of Tallinn University of Technology, Tallinn 12618 Estonia.
Lyudmila V
LV
Chekulayeva
Igor N
IN
Shevchuk
Vladimir A
VA
Chekulayev
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology / Q000628:therapy*; D002374:Catalase / Q000378:metabolism; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use*; D006414:Hematoporphyrin Photoradiation; D006979:Hyperthermia, Induced; D051379:Mice; D010084:Oxidation-Reduction; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D017324:Hematoporphyrin Derivative; D002374:Catalase; D005979:Glutathione Peroxidase