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.
A water-soluble tetra-S-glycosylated porphyrin (P-Glu(4)) 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 microM concentrations necrosis is predominantly observed, while at <10 microM 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-Glu(4) is located in the endoplasmic reticulum at <10 microM. These data indicate that the photodynamic treatment of MDA-MB-231 cells using low concentrations of the P-Glu(4) porphyrin and low light induces apoptosis mostly initiated from stress produced to the endoplasmic reticulum.
Thompson
Sebastian
S
Department of Chemistry and Biochemistry, Hunter College and Graduate Center of the City University of New York, New York, NY 10065, USA.
Chen
Xin
X
Hui
Li
L
Toschi
Alfredo
A
Foster
David A
DA
Drain
Charles Michael
CM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects; D006031:Glycosylation; D006868:Hydrolysis; D007211:Indoles; D008027:Light; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D013194:Staining and Labeling; D013312:Stress, Physiological / Q000187:drug effects / Q000528:radiation effects
D007211:Indoles; D011166:Porphyrins; C007293:DAPI; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D002118:Calcium