5-Aminolevulinic acid enhances cancer radiotherapy in a mouse tumor model

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.

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

“…Several pharmacological strategies have been exploited to develop effective and minimally‐toxic radiosensitizers including small molecules, macromolecules, and nanomaterials . Preclinical studies demonstrated that ALA administration sensitized glioma, melanoma, and colon adenocarcinoma cells to RT through the generation of PPIX and enhanced ROS that have physico‐chemical interactions with the X‐rays being irradiated into malignant cells . To our knowledge, the present study is the first to confirm that adding in vitro single or in vivo repeated administration of exogenous ALA can act as a radio‐sensitizer for prostate adenocarcinoma cells.…”

“…26 Preclinical studies demonstrated that ALA administration sensitized glioma, melanoma, and colon adenocarcinoma cells to RT through the generation of PPIX and enhanced ROS that have physico-chemical interactions with the X-rays being irradiated into malignant cells. 15,24,27 To our knowledge, the present study is the first to confirm that adding in vitro single or in vivo repeated administration of exogenous ALA can act as a radio-sensitizer for prostate adenocarcinoma cells. This result is in agreement with previous studies by other groups.…”

“…Tumor responses to RT and clinical outcomes depend on the intrinsic repair capacity, oxygenation of the tumor tissue, modulation of the tumor microenvironment, and the activation of the immune response, as well as other factors . Several pharmacological strategies have been exploited to develop effective and minimally‐toxic radiosensitizers including small molecules, macromolecules, and nanomaterials .…”

“…22,23 Tumor responses to RT and clinical outcomes depend on the intrinsic repair capacity, oxygenation of the tumor tissue, modulation of the tumor microenvironment, and the activation of the immune response, as well as other factors. 24,25 Several pharmacological strategies have been exploited to develop effective and minimallytoxic radiosensitizers including small molecules, macromolecules, and nanomaterials. 26 Preclinical studies demonstrated that ALA administration sensitized glioma, melanoma, and colon adenocarcinoma cells to RT through the generation of PPIX and enhanced ROS that have physico-chemical interactions with the X-rays being irradiated into malignant cells.…”

Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway

“…It can cause decreased cellular proliferation and increased cytotoxicity such as in treatment of condyloma acuminata and several skin cancers3536. However, low concentrations of ROS after PDT may activate cellular functions of dermal fibroblasts that lead to proliferation and activation of dermal fibroblast for the skin rejuvenation effects37.…”