title: Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin.
abstract: Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound and a sonosensitizer agent. We examined whether 5-aminolevulinic acid (5-ALA)-based SDT at 1 or 3 MHz could enhance the cytotoxicity of bleomycin (BLM) toward mouse mammary tumor cells both in vitro and in vivo. At 1 MHz, cell viability in the 5-ALA-based SDT group at 1, 2, and 3 W/cm(2) was 34.30%, 50.90%, and 60.16%, respectively. Cell viability in the 5-ALA-based SDT+BLM group at 1, 2, and 3 W/cm(2) was 0.09%, 0.32%, and 0.17%, respectively. In contrast, at 3 MHz, 5-ALA-based SDT+BLM did not show pronounced cytotoxicity. In the in vivo study, 5-ALA-based SDT+BLM was significantly more cytotoxic than 5-ALA-based SDT at 1 MHz and 3 MHz. These findings suggest that the mechanism of tumor shrinkage induced by 5-ALA-based SDT+BLM might involve not only direct cell killing, but also vascular shutdown. Thus, we show here that 5-ALA-based SDT enhances the efficacy of BLM both in vitro and in vivo.
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan. Electronic address: tosaki@muses.tottori-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osaki
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: ITO Physiotherapy & Rehabilitation, Tokyo, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Yamanaka
authors.affiliation: ITO Physiotherapy & Rehabilitation, Tokyo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murahata
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuka
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ito
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Imagawa
authors.affiliation: Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Okamoto
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D051379:Mice; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003603:Cytotoxins; D001761:Bleomycin; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid; Bleomycin; Sonodynamic therapy; Ultrasound