Junko Takahashi1, Masaki Misawa2, Hitoshi Iwahashi3. 1. a Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology , Tsukuba , Ibaraki , Japan. 2. b Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology , Tsukuba , Ibaraki , Japan. 3. c Faculty of Applied Biological Sciences , Gifu University , Gifu , Japan.
Abstract
PURPOSE: 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer protoporphyrin (PpIX) used in photodynamic therapy. In our previous work, PpIX enhanced the generation of reactive oxygen species by X-ray irradiation. In this study, we evaluated the potential of ALA as an endogenous sensitizer to X-ray irradiation. METHODOLOGY: Tumor-bearing C57BL/6J mice implanted with B16-BL6 melanoma cells were subsequently treated with irradiation (3 Gy/day for 10 days; total, 30 Gy) plus local administration of 50 mg/kg ALA 24 hours prior to each irradiation (ALA-XT). Tumor-bearing mice without treatment (NT), those treated with ALA only (ALAT), and those treated with X-ray irradiation only (XT) were used as controls. RESULTS: ALA potentiated tumor suppression by X-ray irradiation. In microarray analyses using tumor tissue collected after 10 sessions of fractional irradiation, functional analysis revealed that the majority of dysregulated genes in the XT and ALA-XT groups were related to cell-cycle arrest. Finally, the XT and ALA-XT groups differed in the strength of expression, but not in the pattern of expression. CONCLUSIONS: mRNA analysis revealed that the combined use of ALA and X-ray irradiation sensitized tumors to X-ray treatment. Furthermore, the present results were consistent with ALA's tumor suppressive effects in vivo.
PURPOSE:5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer protoporphyrin (PpIX) used in photodynamic therapy. In our previous work, PpIX enhanced the generation of reactive oxygen species by X-ray irradiation. In this study, we evaluated the potential of ALA as an endogenous sensitizer to X-ray irradiation. METHODOLOGY:Tumor-bearing C57BL/6J mice implanted with B16-BL6 melanoma cells were subsequently treated with irradiation (3 Gy/day for 10 days; total, 30 Gy) plus local administration of 50 mg/kg ALA 24 hours prior to each irradiation (ALA-XT). Tumor-bearing mice without treatment (NT), those treated with ALA only (ALAT), and those treated with X-ray irradiation only (XT) were used as controls. RESULTS:ALA potentiated tumor suppression by X-ray irradiation. In microarray analyses using tumor tissue collected after 10 sessions of fractional irradiation, functional analysis revealed that the majority of dysregulated genes in the XT and ALA-XT groups were related to cell-cycle arrest. Finally, the XT and ALA-XT groups differed in the strength of expression, but not in the pattern of expression. CONCLUSIONS: mRNA analysis revealed that the combined use of ALA and X-ray irradiation sensitized tumors to X-ray treatment. Furthermore, the present results were consistent with ALA's tumor suppressive effects in vivo.
Authors: Sandhya Clement; Ayad G Anwer; Layla Pires; Jared Campbell; Brian C Wilson; Ewa M Goldys Journal: Int J Mol Sci Date: 2021-06-15 Impact factor: 5.923