Regulation of intracellular Ca²⁺ in the cytotoxic response to photodynamic therapy with a chlorin-based photosensitizer

초록

We investigated regulation of intracellular Ca2+ induced by photodynamic therapy (PDT) with a new chlorin-based photosensitizer, DH-II-24, in human gastric adenocarcinoma cells. DH-II-24-mediated PDT induced necrotic cell death according to post-irradiation time, and produced intracellular reactive oxygen species (ROS) in an irradiation time-dependent manner. PDT also increased intracellular Ca2+, and this Ca2+ elevation was largely inhibited by BAPTA-AM but not by EGTA. BAPTA-AM inhibited the ROS production by PDT, whereas NAC and Trolox had no effect on the PDT-induced Ca2+ response. In the presence of EGTA, pre-incubation with thapsigargin, Gly-Phe-beta-naphthylamide or brefeldin A had no significant effect on the PDT-induced elevation in intracellular Ca2+. However, ruthenium red affected the initial and late Ca2+ responses to PDT. Thus, DH-II-24-mediated PDT produces intracellular ROS via elevation in intracellular Ca2+, contributed, at least in part, by mitochondria, which results in necrotic death of the human gastric adenocarcinoma cells.

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