TY - JOUR T1 - 5-Aminolevulinic Acid Enhances Ultrasound-mediated Antitumor Activity <em>via</em> Mitochondrial Oxidative Damage in Breast Cancer JF - Anticancer Research JO - Anticancer Res SP - 3607 LP - 3612 VL - 36 IS - 7 AU - YOSHIKI SHIMAMURA AU - DAI TAMATANI AU - SYOTA KUNIYASU AU - YUSUKE MIZUKI AU - TAKUMA SUZUKI AU - HANAYO KATSURA AU - HISATSUGU YAMADA AU - YOSHIO ENDO AU - TOMOHIRO OSAKI AU - MASAHIRO ISHIZUKA AU - TOHRU TANAKA AU - NOBUYASU YAMANAKA AU - TSUKASA KURAHASHI AU - YOSHIHIRO UTO Y1 - 2016/07/01 UR - http://ar.iiarjournals.org/content/36/7/3607.abstract N2 - 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. ER -