5-Aminolevulinic acid induced apoptosis via oxidative stress in normal gastric epithelial cells.

5-Aminolevulinic acid, a precursor of heme, is utilized in a variety of applications including cancer treatment, surgery, and plant nutrition. However, 5-aminolevulinic acid itself induces oxidative stress and subsequent lipid peroxidation. Reactive oxygen species are factors in oxidative stress, not only causing cellular injury but also inducing several signal transduction pathways. Especially in cancer cells, a significant amount of signalling activation and subsequent activation of protein is caused by the enhancement of reactive oxygen species production. Reactive oxygen species levels in normal cells are low and an oxidative condition is harmful; hence, administration of 5-aminolevulinic acid to normal cells may induce oxidative stress, resulting in cell death. In this study, we investigated the effect of 5-aminolevulinic acid on normal and cancer cells with regard to oxidative stress. We used the rat normal gastric cell line RGM and its cancer-like mutant cell line RGK. 5-Aminolevulinic acid treatment of RGM cells enhanced reactive oxygen species generation and induced apoptosis associated with p53, whereas RGK cells were unaffected. In addition, RGM cell viability was recovered by application of N-acetyl-l-cysteine or p53 inhibitor. These results suggest that 5-aminolevulinic acid causes oxidative stress in normal gastric cells and induces apoptosis via the p53-dependent pathway.