Abstract
5-Aminolevulinic acid (ALA) is a photosensitizer used in photodynamic therapy (PDT) because it causes preferential accumulation of protoporphyrin IX (PpIX) in tumor cells, where it forms singlet oxygen upon light irradiation and kills the tumor cells. Our previous study demonstrated that PpIX enhances generation of reactive oxygen species by physicochemical interaction with X-rays. We investigated the effect of ALA administration with X-ray irradiation of mouse B16-BL6 melanoma cells in vitro and in vivo. ALA facilitates PpIX accumulation in tumor cells and enhances ROS generation in vitro. Tumor suppression significantly improved in animals treated with fractionated doses of radiation (3 Gy × 10; total, 30 Gy) with local administration of 50 mg/kg ALA at 24 h prior to fractional irradiation. These results suggest ALA may improve the efficacy of cancer radiotherapy by acting as a radiomediator.
Highlights
In cancer therapy, radiotherapy is preferred to surgical resection because it is non-invasive, allowing organ structures and functions to remain intact
We hypothesized that protoporphyrin IX (PpIX) accumulation could be induced by adding exogenous Aminolevulinic acid (ALA), and through its generation of reactive oxygen species (ROS) by X-ray irradiation in cancer cells, may act as a radio-mediator of radiotherapy
This study investigated the effect of ALA administration with X-ray irradiation of mouse B16-BL6 melanoma cells in vitro and in vivo
Summary
Radiotherapy is preferred to surgical resection because it is non-invasive, allowing organ structures and functions to remain intact. Photodynamic therapy (PDT) is used to treat certain cancerous and pre-cancerous dermatological conditions It is preferred over surgical resection because it is noninvasive, as is the case for radiotherapy. ROS detection reagents (APF and DHE) and ethanol quencher were used in solutions containing different concentrations of PpIX in the study. This combination of experimental conditions allowed us to estimate the contribution of PpIX to the generation of hydroxyl radical (∙OH), superoxide anion (O2-), and singlet oxygen (1O2). We hypothesized that PpIX accumulation could be induced by adding exogenous ALA, and through its generation of ROS by X-ray irradiation in cancer cells, may act as a radio-mediator of radiotherapy. This study investigated the effect of ALA administration with X-ray irradiation of mouse B16-BL6 melanoma cells in vitro and in vivo
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