title: 5-Aminolevulinic Acid Enhances Ultrasound-mediated Antitumor Activity via Mitochondrial Oxidative Damage in Breast Cancer.
abstract: OBJECTIVE
  5-Aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), is now used for photodynamic therapy (PDT) of pre-cancers of the skin and photodynamic diagnosis (PDD) of brain tumors. Sonodynamic therapy (SDT) of cancers with ultrasound has been studied using 5-ALA as a sonosensitizer. In this article, we evaluated the sonosensitizing activity and mode of action of 5-ALA/PpIX by using mouse mammary tumor EMT6 cells.
  
  
  RESULTS
  5-ALA-SDT showed significant antitumor effects toward EMT6 cells in vitro and in vivo. The fluorescence of MitoSOX Red, an indicator specific for mitochondrial superoxide, was significantly increased by 5-ALA-SDT. Moreover, the fluorescence derived from JC-1, an indicator of mitochondrial membrane potential, was also significantly increased by 5-ALA-SDT. These findings suggest that mitochondria are one of the target organelles of 5-ALA-SDT. PpIX enhanced reactive oxygen species (ROS) production from tert-butyl hydroperoxide (tBHP), suggesting that PpIX might stabilize or promote ROS generation from tBHP.
  
  
  CONCLUSIONS
  5-ALA-SDT showed an antitumor effect in mouse mammary tumor EMT6 cells through oxidation of the mitochondrial membrane via ROS production.
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shimamura
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Tamatani
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Syota
authors.initials: S
authors.lastname: Kuniyasu
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mizuki
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Hanayo
authors.initials: H
authors.lastname: Katsura
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan.
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osaki
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 Co. Ltd., Tokyo, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Yamanaka
authors.affiliation: ITO Co. Ltd., Tokyo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan uto.yoshihiro@tokushima-u.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D000069453:Ultrasonic Waves
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid; mammary tumor; mitochondria; protoporphyrin IX; reactive oxygen species; sonodynamic therapy