Synergistic effect and possible mechanisms of tumor necrosis factor and cisplatin cytotoxicity under moderate hyperthermia against gastric cancer cells

Photosensitization induces intracellular free calcium changes ([Ca2+]i) in some eukaryotic cell systems which either contribute to or protect against cell inactivation. We have investigated whether or not similar changes can be induced in prokaryotes. The skin bacterium Propionibacterium acnes was sensitized using protoporphyrin IX (PP IX) or 5-aminolevulinic acid (ALA). Exogenous ALA resulted in either a preferential accumulation of protoporphyrin (ALA-PP) or of coproporphyrin and/or uroporphyrin (ALA-CP/UP) in P. acnes. For PP IX or ALA-PP sensitization, exposure to broad-band red light resulted in an increase in [Ca2+]i. For ALA-PP sensitization, this increase was transient and [Ca2+]i returned to basal levels within 5-10 min after irradiation. However, the elevated [Ca2+]i levels obtained after PP IX sensitization were maintained for at least 1 h after irradiation. In both cases, the reduction in the external calcium concentration led to an enhancement in the cell survival, indicating that induced [Ca2+]i changes may participate in photoinactivation. Sensitization by hydrophilic coproporphyrin and/or uroporphyrin (ALA-CP/UP) did not affect the [Ca2+]i levels, but higher levels of cell inactivation were obtained. It therefore appears that damage to membrane-associated components is at least partly responsible for [Ca2+]i alterations after photosensitization.