Low concentrations of a non-hydrolysable tetra-S-glycosylated porphyrin and low light induces apoptosis in human breast cancer cells via stress of the endoplasmic reticulum

摘要

A water-soluble tetra-S-glycosylated porphyrin(P-Glu4)is absorbed by MDA-MB-231 human breast cancer cells whereupon irradiation with visible light causes necrosis or apoptosis depending on the concentration of the porphyrin and the power of the light.With the same amount of light irradiation power(9.4 W m~2),at 10-20 mu M concentrations necrosis is predominantly observed,while at <10 mu M concentrations,apoptosis is the principal cause of cell death.Of the various possible pathways for the induction of apoptosis,experiments demonstrate that calcium is released from the endoplasmic reticulum,cytochrome c is liberated from the mitochondria to the cytosol,pro-caspase-3 is activated,poly-(ADP-ribose)polymerase is cleaved,and the chromatin is condensed subsequent to photodynamic treatment of these cells.Confocal microscopy indicates a substantial portion of the P-Glu4 is located in the endoplasmic reticulum at < 10 mu M.These data indicate that the photodynamic treatment of MDA-MB-231 cells using low concentrations of the P-Glu4 porphyrin and low light induces apoptosis mostly initiated from stress produced to the endoplasmic reticulum.