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Molecules 2017, 22(4), 533;

Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro

Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan
Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8506, Japan
SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan
ITO Co., Ltd., Tokyo 176-0014, Japan
Author to whom correspondence should be addressed.
Received: 3 February 2017 / Revised: 18 March 2017 / Accepted: 25 March 2017 / Published: 27 March 2017
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
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Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required. View Full-Text
Keywords: 5-aminolevulinic acid; artesunate; breast cancer; sonodynamic therapy; ultrasound 5-aminolevulinic acid; artesunate; breast cancer; sonodynamic therapy; ultrasound

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Osaki, T.; Uto, Y.; Ishizuka, M.; Tanaka, T.; Yamanaka, N.; Kurahashi, T.; Azuma, K.; Murahata, Y.; Tsuka, T.; Itoh, N.; Imagawa, T.; Okamoto, Y. Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro. Molecules 2017, 22, 533.

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