Mechanism of radiosensitization by porphyrins.
According to our previous data, hematoporphyrin dimethyl ether (HPde) at concentrations useful for photodynamic therapy can radiosensitize aggressive Ehrlich ascite carcinoma (EAT) to 2Gy irradiation inducing total tumour growth inhibition. The aim of this study was to further investigate the possible mechanism of radiosensitization of EAT by dicarboxylic porphyrin-HPde. Our results reveal that HPde is inducing several rearrangements in the EAT cells: 1.2 x 10-6 M of the photosensitizer diminishes the number of cells in mitosis by a factor of 3, increases the number of cells in the S phase of the cell cycle, modifies the activities of antioxidant enzymes glutation S-transferase (GST) and DT-diaphorase (DTD), and eventually induces slight apoptosis. Moreover, it was shown that HPde is a ligand of peripheral benzodiazepine receptor (PBR). Named "house keeper," PBR is usually responsible for all these perturbations, which, in our case, act in concert with the following ionizing radiation, producing the interaction of two antiproliferative/destructive factors.
Luksiene
Zivile
Z
Institute of Materials Sciences and Applied Research, Vilnius University, Sauletekio 9, LT-10223, Vilnius, Lithuania. Zivile.Luksiene@mtmi.vu.lt
Labeikyte
Danute
D
Juodka
Benediktas
B
Moan
Johan
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000532:radiotherapy*; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006415:Hematoporphyrins / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents; D011963:Receptors, GABA-A / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D011838:Radiation-Sensitizing Agents; D011963:Receptors, GABA-A; D004247:DNA; D002374:Catalase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D005982:Glutathione Transferase