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.
Subject(s)
Aminolevulinic Acid/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Mammary Neoplasms, Experimental/drug therapy , Animals , Apoptosis , Cell Line, Tumor , Drug Screening Assays, Antitumor , Female , Humans , Mice , Mice, Inbred BALB C , Mitochondria/drug effects , Mitochondria/metabolism , Neoplasm Transplantation , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Ultrasonic WavesABSTRACT
BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA), precursors of protoporphyrin IX (PpIX), and Sn(IV) chlorin e6 (SnCe6) have been proposed as possible sonosensitizers for sonodynamic therapy of cancer. Therefore, we evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in vivo by using the EMT6/KU tumor-bearing chick embryos. RESULTS: The concentration of PpIX in tumor and liver tissues and serum increased in a time-dependent manner after the i.v. administration of 5-ALA; PpIX concentrations reached their peak level after 5-7 h. The concentration of SnCe6 reached its maximum value in the tumor tissue and serum immediately after i.v. administration. The combined treatment of 5-ALA or SnCe6 with ultrasound irradiation showed a significant antitumor effect towards EMT6/KU solid tumors. CONCLUSION: We evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in a chick embryo model and found that 5-ALA might be more suitable as a sonosensitizer than SnCe6.
