Enhancement of radiosensitivity of oral carcinoma cells by iodinated chlorin p6 copper complex in combination with synchrotron X-ray radiation.

Abstract

The combination of synchrotron X-ray radiation and metal-based radiosensitizer is a novel form of photon activation therapy which offers the advantage of treating malignant tumors with greater efficacy and higher precision than conventional radiation therapy. In this study the anticancer cytotoxic efficacy of a new chlorophyll derivative, iodinated chlorin p6 copper complex (ICp6-Cu), combined with synchrotron X-ray radiation (8-10 keV) in two human oral cancer cell lines is explored. Pre-treatment of cells with 20 µM and 30 µM ICp6-Cu for 3 h was found to enhance the X-ray-induced cytotoxicity with sensitization enhancement ratios of 1.8 and 2.8, respectively. ICp6-Cu localized in cytoplasm, mainly in lysosomes and endoplasmic reticulum, and did not cause any cytotoxicity alone. The radiosensitization effect of ICp6-Cu accompanied a significant increase in the level of reactive oxygen species, damage to lysosomes, inhibition of repair of radiation-induced DNA double-strand breaks, increase in cell death and no significant effect on cell cycle progression. These results demonstrate that ICp6-Cu is a potential agent for synchrotron photon activation therapy of cancer.