Sonodynamically Induced Anti-tumor Effect of 5-Aminolevulinic Acid on Pancreatic Cancer Cells

Abstract Sonodynamic therapy (SDT), a promising modality for cancer treatment, involves the synergistic interaction of ultrasound and some chemical compounds termed sonosensitizers . However, its effect on pancreatic cancer cells remains unclear. In our study, we sought to identify the cytotoxic effects of ultrasound-activated 5- aminolevulinic acid on human pancreatic cancer Capan-1 cells. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) analysis; mitochondrial membrane potential was assessed using the fluorescent probe jc-1; apoptosis was evaluated by flow cytometry; cell morphology was investigated by scanning electron microscopy; apoptosis-related protein expression was analyzed by Western blot assay. We found that SDT significantly decreased the survival rate of cells, and this effect increased with 5- aminolevulinic acid concentration and ultrasound exposure time. The mechanism underlying the effect of SDT involves, in part, the induction of a conspicuous loss in mitochondrial membrane potential and, in part, the induction of apoptosis through upregulation of Bax expression, downregulation of Bcl-2 and increased activation of procaspase-3. These results indicate that the ultrasonically induced cell killing effect could be enhanced by 5-ALA and that the mitochondrial pathway might be involved in the cell damage process. We conclude that SDT is a promising new methodology for pancreatic cancer treatment.