A role for the transient increase of cytoplasmic free calcium in cell rescue after photodynamic treatment.
Chinese hamster ovary (CHO) cells and T24 human bladder transitional carcinoma cells were treated with the photosensitizers aluminum phthalocyanine (AlPc) and hematoporphyrin derivative (HPD), respectively. Exposure of both sensitized cell lines to red light caused an immediate increase of cytoplasmic free calcium, [Ca2+]i, reaching a peak within 5-15 min after exposure and then returning to basal level (approximately 200 nM). The level of the peak [Ca2+]i depended on the light fluence, reaching a maximum of 800-1000 nM at light doses that kill about 90% of the cells. Loading the cells with the intracellular calcium chelators quin2 or BAPTA prior to light exposure enhanced cell killing. This indicates that increased [Ca2+]i after photodynamic therapy (PDT) contributed to survivability of the treated cells by triggering a cellular rescue response. The results of experiments with calcium-free buffer and calcium chelators indicate that both in CHO cells treated with AlPc and with HPD-PDT of T24 cells extracellular Ca2+ influx is mainly responsible for elevated [Ca2+]i. PDT is unique in triggering a cell rescue process via elevated [Ca2+]i. Other cytotoxic agents, e.g., H2O2, produce sustained increase of [Ca2+]i that is involved in the pathological processes leading to cell death.
Penning
L C
LC
University of Leiden, Sylvius Laboratory, Department of Medical Biochemistry, Netherlands.
Rasch
M H
MH
Ben-Hur
E
E
Dubbelman
T M
TM
Havelaar
A C
AC
Van der Zee
J
J
Van Steveninck
J
J
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000502:physiology*; D002132:Calcium Radioisotopes; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002132:Calcium Radioisotopes; D006415:Hematoporphyrins; D007211:Indoles; D009942:Organometallic Compounds; C060570:aluminum phthalocyanine; D000535:Aluminum; D002118:Calcium