Photodynamic therapy induced Fas-mediated apoptosis in human carcinoma cells.

Abstract

Photodynamic therapy (PDT) is a clinical approach that utilizes light-activated drugs for the treatment of a variety of pathologic conditions. Human poorly (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC) cells undergo rapid apoptosis when treated with PDT sensitized with Hypocrellin A (HA) and Hypocrellin B (HB). It has been shown that these compounds have a strong photodynamic effect on tumors and viruses. The initiating events of PDT sensitized HA and HB-induced apoptosis are poorly defined. In the current study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HA and HB-treated PDT induced apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome c, involvement of caspases-8 and -3 and the status caspase-3 specific substrate PARP, were evaluated in PDT treated tumor cells. Photoactivation of HA and HB enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell death in all tumor cell lines studied. CD95/ CD95L expression appeared within 2 h following light activation and appeared to be a primary event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm is a secondary event following the activation of initiator caspase-8 preceding caspase-3 activation, cleavage of PARP and DNA fragmentation. Cytochrome c appeared in the cytosol within 2-3 h post PDT. Cleavage of PARP was observed at 3-4 h following PDT and caspase-3 specific inhibitor DEVD-CHO and broad-spectrum caspases inhibitor z-VAD-fmk blocked caspase-3 activation and PARP cleavage suggesting that caspase-3 plays an important role in HA and HB-induced apoptosis.

• Authors: Seyed Mohamed Ali, Soo Khee Chee, Gan Yik Yuen, Malini Olivo
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 9 Issue 3 Pg. 257-70 (Mar 2002) ISSN: 1107-3756 [Print] Greece
• PMID: 11836632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytochrome c Group
• FASLG protein, human
• Fas Ligand Protein
• Membrane Glycoproteins
• Photosensitizing Agents
• Quinones
• fas Receptor
• Phenol
• Perylene
• CASP3 protein, human
• Caspase 3
• Caspases
• hypocrellin A

Topics

• Apoptosis (drug effects)
• Carcinoma (metabolism, pathology, therapy)
• Caspase 3
• Caspases (metabolism)
• Cytochrome c Group (metabolism)
• Fas Ligand Protein
• Humans
• Membrane Glycoproteins (metabolism)
• Membrane Potentials (drug effects)
• Mitochondria (drug effects, metabolism)
• Nasopharyngeal Neoplasms (metabolism, pathology, therapy)
• Perylene (administration & dosage, analogs & derivatives)
• Phenol
• Photochemotherapy
• Photosensitizing Agents (administration & dosage)
• Quinones (administration & dosage)
• Tumor Cells, Cultured
• fas Receptor (metabolism)