BAM-SiPc, a novel agent for photodynamic therapy, induces apoptosis in human hepatocarcinoma HepG2 cells by a direct mitochondrial action.
Photodynamic therapy is recently developed as an effective treatment for malignant disease. The therapeutic effect depends on the properties of the photosensitizers. Among the novel photosensitizers we have synthesized, the unsymmetrical bisamino phthalocyanine, SiPc[C3H5(NMe2)2O](OMe) (BAM-SiPc) is particularly active in the HepG2 cell culture model. Fluorescence microscopy has also indicated that it targets the mitochondria. In the present investigation, the biochemical mechanisms of BAM-SiPc leading to cell death were investigated. Photodynamic treatment with BAM-SiPc resulted in the generation of reactive oxygen species and a collapse of mitochondrial membrane potential. The proapoptotic Bax protein was translocated from the cytosol to mitochondria; while the level of the mitochondrial anti-apoptotic Bcl-2 protein decreased after photodynamic treatment. Cytochrome c, but not apoptosis-inducing factor, was released from the mitochondria into the cytosol, subsequently resulting in the cleavage of poly(ADP-ribose) polymerase. These events were at least partially responsible for the observed BAM-SiPc induced apoptosis, which was clearly demonstrated by (a) the loss of membrane asymmetry, (b) DNA ladder formation, and (c) the presence of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells.
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Janice C
JC
Lai
Pui-Chi
PC
Lo
Dennis K P
DK
Ng
Wing-Hung
WH
Ko
Stanley C H
SC
Leung
Kwok-Pui
KP
Fung
Wing-Ping
WP
Fong
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D017646:Organosilicon Compounds / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species
C516359:BAM-SiPc; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species