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+)](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.
Hong
Xin
X
Department of Neurosurgery, Henry Ford Hospital, Detroit, MI 48202, USA.
Jiang
Feng
F
Kalkanis
Steven N
SN
Zhang
Zheng Gang
ZG
Zhang
Xuepeng
X
Zheng
Xuguang
X
Jiang
Hao
H
Chopp
Michael
M
D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D019284:Thapsigargin / Q000494:pharmacology
D017319:Photosensitizing Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019284:Thapsigargin; D017323:Dihematoporphyrin Ether; D002118:Calcium