5-Aminolevulinic Acid Enhances Ultrasound-mediated Antitumor Activity via Mitochondrial Oxidative Damage in Breast Cancer.

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.

• Authors: Yoshiki Shimamura, Dai Tamatani, Syota Kuniyasu, Yusuke Mizuki, Takuma Suzuki, Hanayo Katsura, Hisatsugu Yamada, Yoshio Endo, Tomohiro Osaki, Masahiro Ishizuka, Tohru Tanaka, Nobuyasu Yamanaka, Tsukasa Kurahashi, Yoshihiro Uto
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 7 Pg. 3607-12 (Jul 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27354630 (Publication Type: Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Reactive Oxygen Species
• Aminolevulinic Acid

Topics

• Aminolevulinic Acid (administration & dosage)
• Animals
• Antineoplastic Agents (administration & dosage)
• Apoptosis
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Female
• Humans
• Mammary Neoplasms, Experimental (drug therapy)
• Mice
• Mice, Inbred BALB C
• Mitochondria (drug effects, metabolism)
• Neoplasm Transplantation
• Oxidation-Reduction
• Reactive Oxygen Species (metabolism)
• Ultrasonic Waves