HPD-induced photodynamic changes in intracellular cyclic AMP levels in human bladder transitional carcinoma cells, clone T24.
Human bladder transitional carcinoma cells, clone T24, were incubated with hematoporphyrin derivative and subsequently exposed to red light. Immediately after light exposure a light-dose dependent increase in intracellular cyclic AMP levels was observed. The concentrations decreased to non-treated levels within 2 h after illumination. Inhibition of cyclooxygenase with indomethacin reduced the increase drastically, whereas the presence of PGE2 enhanced the production of cyclic AMP. PGE2, 8'-bromo-cyclic AMP and a direct stimulation of adenylyl cyclase by forskolin reduced the photodynamically induced cell killing. On the other hand, suppression of cyclic AMP by the cyclooxygenase inhibitor indomethacin, enhanced the photodynamically induced cell killing. Therefore, it is suggested that cyclic AMP production in T24 cells is a step in a cellular rescue pathway, resulting in protection against photodynamic cell killing.
Sylvius Laboratory, Dept. of Medical Biochemistry, Leiden, The Netherlands.
L C
LC
Penning
J
J
VanSteveninck
T M
TM
Dubbelman
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D016923:Cell Death / Q000528:radiation effects*; D000242:Cyclic AMP / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D017324:Hematoporphyrin Derivative / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008027:Light; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017324:Hematoporphyrin Derivative; D000242:Cyclic AMP; D015232:Dinoprostone; D007213:Indomethacin