Apoptosis of SAS cells induced by sonodynamic therapy using 5-aminolevulinic acid sonosensitizer

Background: 5-Aminolevulinic acid (ALA) has been used as a photodynamic sensitizer for cancer treatment using photodynamic therapy. However, the light has markedly limited penetration depth. It was found that ALA also responds to low energy ultrasound, which has the capability to penetrate deep into tissues. Therefore, sonodynamic therapy (SDT) is a promising method for noninvasive treatment of tumors embedded deep in the tissue. It is desirable to kill the cancer cells via apoptosis rather than necrosis, and therefore, it is necessary to gain a better understanding of the mechanisms of treating cancer using SDT. Materials and Methods: The apoptosis of SAS cells induced by pulsed 1.05MHz ultrasound in combination with ALA was investigated in vitro. Results: The cells exposed to SDT with 10 μg/ml ALA displayed significantly higher apoptosis than cells treated by ultrasound alone. There was notably increased reactive oxygen species (ROS) production in the cells treated by SDT with ALA than by ultrasound alone, resulting in higher lipid peroxidation (LPO) level and more cells losing their mitochondrial membrane potential (MMP). Conclusion: ALA-mediated SDT produced strong apoptotic effects on SAS cells, which were mainly related to the excessive intracellular ROS production followed by LPO increase and MMP decrease.