title: Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro.
abstract: 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.
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. tosaki@muses.tottori-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osaki
authors.affiliation: Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8506, Japan. kazu-azuma@muses.tottori-u.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan. ymurahata@muses.tottori-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan. tsuka@muses.tottori-u.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: ITO Co., Ltd., Tokyo 176-0014, Japan. taromobile@me.com.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Yamanaka
authors.affiliation: ITO Co., Ltd., Tokyo 176-0014, Japan. imagawat@muses.tottori-u.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. yokamoto@muses.tottori-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. uto.yoshihiro@tokushima-u.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murahata
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. mishizuk@sbigroup.co.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuka
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. tortanaka@sbigroup.co.jp.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Itoh
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. yamanaka@itolator.co.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Imagawa
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. kurahashi@itolator.co.jp.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Okamoto
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D066298:In Vitro Techniques; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000628:therapy; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014464:Ultrasonic Therapy / Q000379:methods
chemical_list: D037621:Artemisinins; D017382:Reactive Oxygen Species; D000077332:Artesunate; D000622:Aminolevulinic Acid
keywords: 5-aminolevulinic acid; artesunate; breast cancer; sonodynamic therapy; ultrasound