Photodynamic stimulation causes sustained increase in intracellular calcium concentration in cells of small cell lung carcinoma.
Photodynamic agents, due to their selective uptake by tumor cells and photon-dependent selective activation, have immense implications for cancer treatment. The present study provided direct evidence that the photon activation of chloro-aluminum phthalocyanine sulphonate (A1PcS4) in the presence of extracellular Ca2+ caused a rapid increase followed by a sustained increase in intracellular concentration of calcium ion ([Ca2+]i) in a small cell lung carcinoma (SCLC) cell line, SBC-3. The [Ca2+]i increase by photodynamic stimulation was completely inhibited by the removal of extracellular Ca2+ and reintroduction of extracellular Ca2+ immediately led to a rapid elevation of [Ca2+]i. However, the increase was not inhibited by application of Ni2+, nifedipine, or SK&F 96365, a receptor-mediated and voltage-dependent Ca2+ entry blocker. The photosensitizer A1PcS4 alone or light alone (4 min) had no effect on [Ca2+]i. Cytotoxicity examination by trypan blue exclusion test, however, suggested photodynamic stimulation-induced cell injury which was observed in both the presence and the absence of extracellular Ca2+. These results indicate that [Ca2+]i increase may not be mandatory for photodynamic stimulation-induced cell injury. Whether [Ca2+]i increase can accelerate, at least in part, cell death under the physiological condition, whether the mechanism(s) of cell death can be different in the presence and the absence of extracellular Ca2+, and whether [Ca2+]i increase can be totally unrelated to cell death await further work.
Hayashi
M
M
Department of Biomedical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kanno
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism*; D016210:Methacholine Chloride / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D007093:Imidazoles; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D016210:Methacholine Chloride; C048577:aluminum tetrasulfophthalocyanine; D001285:Atropine; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium