CALCIUM-DEPENDENT PHOTODYNAMIC-ACTION OF DISULFONATED AND TETRASULFONATED ALUMINUM PHTHALOCYANINE ON NORMAL AND TUMOR-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 stu dy amylase release has been used to assess the mechanisms by which the photodynamic drugs tetra- and disulphonated aluminium phthalocyanine (A1PcS(4), A1PcS(2)) act on pancreatic cells via energy and calcium-de pendent activation and transduction pathways. The photodynamic release of amylase was found to be energy dependent and inhibited by the chel ation of free cytoplasmic calcium but not by the removal of extracellu lar calcium. In contrast to their effects on normal acinar cells, the photodynamic action of A1PcS(4) and A1PcS(2) was to inhibit amylase se cretion from pancreatoma AR4-2J cells. Removal of extracellular calciu m reversed this inhibitory efect on AR4-2J cells and produced a signif icant increase in amylase release, but chelation of free cytoplasmic c alcium did not affect the inhibitory photodynamic action of the phthal ocyanines on amylase release from the tumour cells. Overall, these res ults demonstrate further important distinctions between the photodynam ic action of sulphonated aluminium phthalocyanines on normal versus tu mour exocrine cells of the pancreas and indicate that calcium plays an important role in photodynamic drug action, since these agents affect ed intracellular calcium mobilisation at some distal point in the memb rane 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.