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

Abstract

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+)](i)). Thapsigargin, which increased [Ca(2+)](i), 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+)](i) 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+)](i) 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+)](i) plays an important role in PDT-induced enzymatic cell detachment decrease and cytotoxicity. Cell migration may be affected by these changes.

• Authors: Xin Hong, Feng Jiang, Steven N Kalkanis, Zheng Gang Zhang, Xuepeng Zhang, Xuguang Zheng, Hao Jiang, Michael Chopp
• Journal: Lasers in medical science (Lasers Med Sci) Vol. 24 Issue 5 Pg. 777-86 (Sep 2009) ISSN: 1435-604X [Electronic] England
• PMID: 19198972 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Photosensitizing Agents
• 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
• Egtazic Acid
• Thapsigargin
• Dihematoporphyrin Ether
• Calcium

Topics

• Calcium (metabolism)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Dihematoporphyrin Ether (therapeutic use)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Glioma (drug therapy, metabolism, pathology)
• Humans
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Thapsigargin (pharmacology)