PT  - JOURNAL ARTICLE
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
TI  - 5-Aminolevulinic Acid Enhances Ultrasound-mediated Antitumor Activity <em>via</em> Mitochondrial Oxidative Damage in Breast Cancer
DP  - 2016 Jul 01
TA  - Anticancer Research
PG  - 3607--3612
VI  - 36
IP  - 7
4099  - http://ar.iiarjournals.org/content/36/7/3607.short
4100  - http://ar.iiarjournals.org/content/36/7/3607.full
SO  - Anticancer Res2016 Jul 01; 36
AB  - 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.