Acetic acid enhances the effect of photodynamic therapy in gastric cancer cells via the production of reactive oxygen species.

Acetic acid is a major component of vinegar and is reported to have beneficial health effects. Notably, it causes oxidative stress and enhances the production of reactive oxygen species (ROS) in gastric cancer cells. ROS play important roles in cellular signal transduction, resulting in the regulation of protein expression and apoptosis. We previously reported that ROS upregulate heme carrier protein 1 (HCP1). Moreover, ROS increase the cellular uptake of porphyrins, which are precursors of heme and substrates for uptake by HCP1. Therefore, we hypothesized that photodynamic therapy (PDT) for cancer treatment using laser irradiation and photosensitizers, such as porphyrin, is enhanced via ROS produced by acetic acid. Herein, we used the rat gastric mucosal cells, RGM1, its cancer-like mutated cells, RGK1, and a manganese superoxide dismutase (MnSOD)-overexpressing RGK cell line, RGK-MnSOD. We confirmed that cancer-specific cellular uptake of porphyrin is increased upon acetic acid treatment and enhances the PDT cytotoxicity in RGK-1, not in RGM-1 and RGK-MnSOD. We believe that this occurs because of the overproduction of ROS and subsequent upregulation of HCP1 in cancerous cells. In conclusion, acetic acid can elevate the effect of PDT by inducing cancer-specific HCP1 expression via ROS production.