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Communication

Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model

1
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8566, Japan
2
Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
3
Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5155; https://doi.org/10.3390/ijms20205155
Received: 4 September 2019 / Revised: 12 October 2019 / Accepted: 16 October 2019 / Published: 17 October 2019
(This article belongs to the Special Issue Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches)
Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, (“radiodynamic therapy (RDT)”), instead of with 5-ALA and laser beams (“photodynamic therapy”), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ∙OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy. View Full-Text
Keywords: radiotherapy; radiodynamic therapy; melanoma; brain metastases; 5-aminolevurinic acid; protoporphyrin IX; photodynamic therapy; DNA double-strand break radiotherapy; radiodynamic therapy; melanoma; brain metastases; 5-aminolevurinic acid; protoporphyrin IX; photodynamic therapy; DNA double-strand break
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MDPI and ACS Style

Takahashi, J.; Nagasawa, S.; Ikemoto, M.J.; Sato, C.; Sato, M.; Iwahashi, H. Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model. Int. J. Mol. Sci. 2019, 20, 5155. https://doi.org/10.3390/ijms20205155

AMA Style

Takahashi J, Nagasawa S, Ikemoto MJ, Sato C, Sato M, Iwahashi H. Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model. International Journal of Molecular Sciences. 2019; 20(20):5155. https://doi.org/10.3390/ijms20205155

Chicago/Turabian Style

Takahashi, Junko, Shinsuke Nagasawa, Mitsushi J. Ikemoto, Chikara Sato, Mari Sato, and Hitoshi Iwahashi. 2019. "Verification of 5-Aminolevurinic Radiodynamic Therapy Using a Murine Melanoma Brain Metastasis Model" International Journal of Molecular Sciences 20, no. 20: 5155. https://doi.org/10.3390/ijms20205155

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