Yoshiki Shimamura1, Dai Tamatani1, Syota Kuniyasu1, Yusuke Mizuki1, Takuma Suzuki1, Hanayo Katsura1, Hisatsugu Yamada1, Yoshio Endo2, Tomohiro Osaki3, Masahiro Ishizuka4, Tohru Tanaka4, Nobuyasu Yamanaka5, Tsukasa Kurahashi5, Yoshihiro Uto6. 1. Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan. 2. Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. 3. Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan. 4. SBI Pharmaceuticals Co. Ltd., Tokyo, Japan. 5. ITO Co. Ltd., Tokyo, Japan. 6. Department of Life System, Institute of Technology and Science, Graduate School, Tokushima University, Tokushima, Japan uto.yoshihiro@tokushima-u.ac.jp.
Abstract
BACKGROUND/AIM: 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. CONCLUSION: 5-ALA-SDT showed an antitumor effect in mouse mammary tumor EMT6 cells through oxidation of the mitochondrial membrane via ROS production. Copyright
BACKGROUND/AIM: 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. CONCLUSION:5-ALA-SDT showed an antitumor effect in mouse mammary tumor EMT6 cells through oxidation of the mitochondrial membrane via ROS production. Copyright