Sensitization of rat C6 glioma cells to ionizing radiation by porphyrins

Abstract

Background. Radiosensitizers are used in order to increase the efficacy of radiotherapy. Most of the presently known radiosensitizing agents have a poor selectivity and are not tumour-specific. Porphyrins have a selective uptake in tumour relative to the surrounding normal tissue. The aim of the present work was to test the capability of two photosensitizers-hematoporphyrin derivative (HpD) or temoporfin (mTHPC)-and gamma rays to produce some kind of selective inhibition of tumour cell proliferation. Materials and methods. Dark toxicity experiments were carried out using a sensitizer concentration range 0-50 µg/ml for HpD, or 0-5 µg/ml for mTHPC. For the radiosensitized treatment of rat C6 glioma cells, HpD was added at a final concentration of 1 µg/ml and mTHPC at a final concentration of 0.1 µg/ml. The irradiation with gamma rays was performed using doses ranging from 0 to 8 Gy. Cell survival was determined using the colony forming assay. Results. HpD (1 µg/ml) and mTHPC (0.1 µg/ml) were found to have no toxic effects on C6 glioma cells. A cytotoxic dose without drugs, inducing a reduction in colony survival by 20%, was achieved at 2 Gy and by 50% at 4 Gy. The radiosensitized treatment of cells with HpD resulted in a significant (p ≤ 0.05) decline in cell survival as compared with irradiation alone. For C6 treated with mTHPC, the results did not differ between the two groups (with and without the drug). Conclusions. The results of this study have shown that mTHPC (0.1 µg/ml) does not act as a radiosensitizer, whereas HpD can act, under certain conditions, as a tumour radiosensitizer. These findings suggest that HpD is a potential agent in combination with radiation therapy of malignant gliomas.

Photodynamic therapy: Innovative approaches for antibacterial and anticancer treatments

“…Some reports suggested that a combined use of PDT and ionizing radiation in cancer treatment could be more beneficial than using each of them separately. 239 However, it was described that a combined therapy of ionizing radiation and PDT did not show satisfactory results with PSs that tend to localize in the cytoplasm as the main target of radiotherapy is DNA. 236,240,241 In recent years, there has been a growing interest in the use of semiconducting materials for biomedical applications, including imaging and therapy.…”

“…Integrating ionizing radiation into PDT seems beneficial due to the ability of certain PSs to acts as radiosensitizers. Some reports suggested that a combined use of PDT and ionizing radiation in cancer treatment could be more beneficial than using each of them separately 239 . However, it was described that a combined therapy of ionizing radiation and PDT did not show satisfactory results with PSs that tend to localize in the cytoplasm as the main target of radiotherapy is DNA 236,240,241 …”

Radiodynamic Therapy with Chlorine-Based Photosensitizer on Pliss Lymphosarcoma Solid Tumor: In Vivo Experiment

“…Of particular interest are studies into the radiosensitizing properties of PS used in PDT. The first PS whose radiosensitizing activity was proved in experimental studies in vitro and in vivo were «Hematoprophyrin» and «Photofrin II» [8,9,10]. At the moment, researchers are especially interested in studying the radiosensitizing properties of 5-ALA which itself is not a PS, but it can be converted into a natural PSprotoporphyrin IX (PpIX) [1,2,3].…”

Combined photodynamic and radiodynamic therapy with a chlorine photosensitizer under fractionated radiation exposure to transplanted tumors in an <i>in vivo</i> experiment

“…В источниках литературы, опубликованных в период с начала 2000-х гг. до 2019 г., встречаются немногочисленные публикации, посвященные изучению радиодинамической активности ФС «Протопорфирин IX» (ПпIX), «Дериват гематопорфирина» и «Порфимер содиум» в экспериментах in vitro / in vivo (глиомы c6 и U-373 MG, глиосаркома 9L; плоскоклеточная карцинома пищевода человека ОE-21, аденокарцинома пищевода человека OE-33; карцинома мочевого пузыря человека RT4 и аденонокарцинома толстого кишечника HT-29) [13][14][15][16].…”