Calcium-dependent photodynamic action of di- and tetrasulphonated aluminium phthalocyanine on normal and tumour-derived rat pancreatic exocrine cells.
Important differences exist in the responses to photodynamic agents of normal and tumour-derived pancreatic acinar cells. In the present study amylase release has been used to assess the mechanisms by which the photodynamic drugs tetra- and disulphonated aluminium phthalocyanine (A1PcS4, A1PcS2) act on pancreatic cells via energy and calcium-dependent activation and transduction pathways. The photodynamic release of amylase was found to be energy dependent and inhibited by the chelation of free cytoplasmic calcium but not by the removal of extracellular calcium. In contrast to their effects on normal acinar cells, the photodynamic action of A1PcS4 and A1PcS2 was to inhibit amylase secretion from pancreatoma AR4-2J cells. Removal of extracellular calcium reversed this inhibitory effect on AR4-2J cells and produced a significant increase in amylase release, but chelation of free cytoplasmic calcium did not affect the inhibitory photodynamic action of the phthalocyanines on amylase release from the tumour cells. Overall, these results demonstrate further important distinctions between the photodynamic action of sulphonated aluminium phthalocyanines on normal versus tumour exocrine cells of the pancreas and indicate that calcium plays an important role in photodynamic drug action, since these agents affected intracellular calcium mobilisation at some distal point in the membrane signal transduction pathway for regulated secretion. Furthermore, the photodynamic inhibition of constitutive secretion in tumour cells may involve a calcium-dependent membrane target site or modulation of membrane calcium channels by activation of protein kinase C.
al-Laith
M
M
Department of Pharmacology, University of Cambridge, UK.
Matthews
E K
EK
D000681:Amylases / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D018267:Carcinoma, Acinar Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009840:Oligomycins / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D007211:Indoles; D009840:Oligomycins; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; D018723:Bethanechol; C048577:aluminum tetrasulfophthalocyanine; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D000968:Antimycin A; C064331:aluminum phthalocyanine disulfonate; D003847:Deoxyglucose; D000681:Amylases; D012844:Sincalide; D002118:Calcium