Intracellular free calcium mediates glioma cell detachment and cytotoxicity after photodynamic therapy.

Photofrin photodynamic therapy (PDT) caused a dose-dependent decrease of enzymatic cell detachment by trypsin/ethylenediamine tetra-acetic acid (EDTA) in human glioma U251n and U87 cells. This happened coincidently with the increase of intracellular free calcium (Ca(2+)). Thapsigargin, which increased Ca(2+), induced further decrease in enzymatic cell detachment and increased cytotoxicity. Opposite effects were observed when 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid tetrakis, an intracellular Ca(2+) chelator, was used. PDT-induced changes in Ca(2+) and cell detachment were not blocked by calcium channel antagonists nickel (Ni(2+)) or nimodipine, nor were they altered when cells were irradiated in a buffer free from Ca(2+) and magnesium (Mg(2+)), suggesting that Ca(2+) is derived from the internal calcium stores. Decreased cell migration was observed after PDT, as assessed by chemotactic and wound-healing assays. Our findings indicated that internal calcium store-derived Ca(2+) plays an important role in PDT-induced enzymatic cell detachment decrease and cytotoxicity. Cell migration may be affected by these changes.