Radiosensitization of tumours by porphyrins

• Published in: Cancer letters 2006-04, Vol.235 (1), p.40-47
• Main Authors: Luksiene, Zivile, Juzenas, Petras, Moan, Johan
• Format: Article
• Language: English
• Subjects: Aggressive tumours; Animals; Bladder cancer; Cancer therapies; Carcinoma, Ehrlich Tumor - radiotherapy; Dihematoporphyrin Ether - therapeutic use; Drug dosages; Efficiency; Experiments; Female; Hematoporphyrins - therapeutic use; Liver Neoplasms, Experimental - radiotherapy; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Photochemotherapy; Photosensitization; Porphyrins; Radiation therapy; Radiation, Ionizing; Radiation-Sensitizing Agents - therapeutic use; Radiosensitization; Radiotherapy Dosage; Receptors, GABA-A - metabolism; Rodents; Studies; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.03.041

Our previous data indicate, that hematoporphyrin dimethyl ether (HPde) can totally inhibit the growth of aggressive Ehrlich ascite tumour, when combined with low doses (2 Gy) of ionizing radiation. Taking into account these findings, it appears of particular interest to evaluate the dependence of radiosensitizing efficiency of porphyrins on tumour aggressiveness. For this purpose two experimental tumour models (aggressive murine Ehrlich ascite carcinoma, (EAT), and not-aggressive hepatoma MH-22A) were used. Moreover, radiosensitizing properties of three porphyrin-type compounds of different chemical heterogeneity were evaluated (hematoporphyrin dimethyl ether (HPde), photofrin II (PII) and hematoporphyrin derivative (HPD)). Data obtained indicate, that HPde is the most effective one in this context (HPde>PII>HPD). It is important to note, that only the aggressive EAT tumours were radiosensitized by these dyes. No signs of radiosensitization (inhibition of tumour growth, injury of tumour tissue, evaluated by histological analysis) were observed in not-aggressive MH-22A hepatoma. Moreover, it was shown, that ligands of peripheral benzodiazepine receptors (PBR) might diminish the cell growth in aggressive EAT, but not in not-aggressive MH-22A hepatoma. The mechanism of radiosensitization by porphyrins, proposed in our previous studies, was strongly confirmed by these data. Actually, dicarboxylic porphyrins, being ligands of PBR, which are highly expressed in just aggressive tumours, can inhibit tumour cell proliferation and act in concert with ionizing radiation. Thus, combination of porphyrin and ionising radiation reflects the action of two antiproliferative factors, what eventually increases the response of aggressive tumours to the low doses of ionising radiation.