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Anticancer Res ; 38(7): 4313-4317, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29970567

ABSTRACT

BACKGROUND/AIM: Carbon-ion beam is one of the most advanced radiations used for cancer treatment. However, there are tumors that are difficult to suppress with carbon-ion beam alone, thus necessitating development of drugs that can enhance its therapeutic effect. In this regard, the radiosensitizing effect of 5-aminolevulinic acid (ALA) and protoporphyrin IX (PpIX), that is a metabolic intermediate of ALA, on carbon-ion beam was investigated. MATERIALS AND METHODS: Radiosensitizing activity, mitochondrial ROS and DNA double-strand break production of ALA and PpIX were evaluated by irradiation with 1.0 or 1.5-Gy carbon-ion beam to mouse mammary EMT6 tumor cells. RESULTS: Combination of carbon-ion beam and ALA or PpIX showed a significant enhancement of its cytotoxic activity through a significant increase in ROS production in mitochondria. Furthermore, the combined activity of carbon-ion beam and ALA resulted in a significant increase in DNA double-strand breakage. CONCLUSION: ALA selectively accumulates in the mitochondria and PpIX synthesized from ALA reacts with carbon-ion beam to produce ROS that exert antitumor activity.


Subject(s)
Heavy Ion Radiotherapy/methods , Levulinic Acids/pharmacology , Protoporphyrins/pharmacology , Radiation-Sensitizing Agents/pharmacology , Animals , Cell Line, Tumor , DNA Breaks, Double-Stranded/radiation effects , Mice , Reactive Oxygen Species/radiation effects , Aminolevulinic Acid
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