CALCIUM-DEPENDENT PHOTODYNAMIC-ACTION OF DISULFONATED AND TETRASULFONATED ALUMINUM PHTHALOCYANINE ON NORMAL AND TUMOR-DERIVED RAT PANCREATIC EXOCRINE CELLS
M. Allaith et Ek. Matthews, CALCIUM-DEPENDENT PHOTODYNAMIC-ACTION OF DISULFONATED AND TETRASULFONATED ALUMINUM PHTHALOCYANINE ON NORMAL AND TUMOR-DERIVED RAT PANCREATIC EXOCRINE CELLS, British Journal of Cancer, 70(5), 1994, pp. 893-899
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.