Photodynamic inhibition of enzymatic detachment of human cancer cells from a substratum.
Photodynamic therapy (PDT) is currently used for cancer treatment. It is shown that sublethal PDT of human WiDr adenocarcinoma cells and D54Mg glioblastoma cells with 5-aminolevulinic acid (ALA), disulfonated tetraphenylporphyrine (TPPS(2a)), or MitoTracker Red (MTR) inhibits their trypsin-induced detachment from a plastic substratum. TPPS(2a) was bound selectively to the plasma membrane, whereas MTR was found in mitochondria. Both granular and diffuse fluorescence of ALA-derived protoporphyrin IX (PpIX) was observed in the perinuclear cytoplasm but not in the plasma membrane of WiDr cells stained for 2 h with 1 mM ALA. In D54Mg cells, PpIX fluorescence was observed not only in the cytoplasm but also in the plasma membrane. Fluorescence measurements showed a progressive accumulation of PpIX in the WiDr cells during incubation with ALA and a PpIX efflux into the medium after 1 h or longer incubation. PpIX retained in the plasma membrane during efflux may be responsible for PDT-induced impairment of cell adhesion. On the other hand, MTR-PDT or ALA-PDT after 15-min incubation, when the newly synthesized PpIX should remain in mitochondria, also inhibited enzymatic cell detachment. Therefore, photodynamic targeting of mitochondria, remote from the cell surface where adhesion occurs, may disturb cell adhesion. Photodynamic inhibition of enzymatic cell detachment may be related to PDT-induced inhibition of tumour metastasis.
Uzdensky
Anatoly
A
Institute for Cancer Research, 0310 Montebello, Oslo, Norway. uzd@krinc.ru
Juzeniene
Asta
A
Ma
Li-Wei
LW
Moan
Johan
J
D000230:Adenocarcinoma; D000622:Aminolevulinic Acid / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes / Q000494:pharmacology; D005909:Glioblastoma; D006801:Humans; D008856:Microscopy, Fluorescence; D009930:Organic Chemicals; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000032:analysis / Q000737:chemistry; D012402:Rotenone / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D005456:Fluorescent Dyes; D009930:Organic Chemicals; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D014361:Trypsin Inhibitors; C425082:di(4-sulfonatophenyl)diphenylporphine; C107472:red dye CMXRos; D012402:Rotenone; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D014357:Trypsin