PMID- 16481739 OWN - NLM STAT- MEDLINE DCOM- 20070123 LR - 20200930 IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 5 IP - 4 DP - 2006 Apr TI - BAM-SiPc, a novel agent for photodynamic therapy, induces apoptosis in human hepatocarcinoma HepG2 cells by a direct mitochondrial action. PG - 413-8 AB - 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. FAU - Lai, Janice C AU - Lai JC AD - Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. FAU - Lo, Pui-Chi AU - Lo PC FAU - Ng, Dennis K P AU - Ng DK FAU - Ko, Wing-Hung AU - Ko WH FAU - Leung, Stanley C H AU - Leung SC FAU - Fung, Kwok-Pui AU - Fung KP FAU - Fong, Wing-Ping AU - Fong WP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060414 PL - United States TA - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (BAM-SiPc) RN - 0 (Indoles) RN - 0 (Organosilicon Compounds) RN - 0 (Photosensitizing Agents) RN - 0 (Reactive Oxygen Species) SB - IM MH - *Apoptosis MH - Carcinoma, Hepatocellular/*pathology/*therapy MH - Cell Line, Tumor MH - Cell Survival MH - Humans MH - In Situ Nick-End Labeling MH - Indoles/*pharmacology MH - Membrane Potentials/drug effects MH - Microscopy, Fluorescence MH - Mitochondria/*metabolism MH - Organosilicon Compounds/*pharmacology MH - Photochemotherapy/*methods MH - Photosensitizing Agents/*pharmacology MH - Reactive Oxygen Species EDAT- 2006/02/17 09:00 MHDA- 2007/01/24 09:00 CRDT- 2006/02/17 09:00 PHST- 2006/02/17 09:00 [pubmed] PHST- 2007/01/24 09:00 [medline] PHST- 2006/02/17 09:00 [entrez] AID - 2513 [pii] AID - 10.4161/cbt.5.4.2513 [doi] PST - ppublish SO - Cancer Biol Ther. 2006 Apr;5(4):413-8. doi: 10.4161/cbt.5.4.2513. Epub 2006 Apr 14.