Photodynamic-induced apoptosis of human nasopharyngeal carcinoma cells using Hypocrellins.

Abstract

It has been reported that novel photosensitizers Hypocrellin A and B, lipid soluble perylquinone derivatives of the genus Hypericum have a strong photodynamic effect on tumors and viruses. The molecular mechanisms of tumor cell death induction by Hypocrellin A and B are poorly understood. In this study, we have examined the photodynamic effects of Hypocrellin A and B compounds in poorly differentiated (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC) cells. Using these cell lines we investigated the role of the apoptotic pathway in photosensitized Hypocrellin A and B-mediated cell death. Tumor cells photoactivated with Hypocrellin A and B showed cell size shrinkage and an increase in the sub-diploid DNA content. A loss of membrane phospholipid asymmetry associated with apoptosis was induced by both tumor cell lines as evidenced by the externalization of phosphatidylserine (PS). A dose-dependent increase in caspases-3 protease activity inhibitable by the tetrapeptide inhibitor DEVD-CHO was also observed in both cell lines. Western blot analysis of poly (ADP-ribose) polymerase, a caspase substrate, showed the classical cleavage pattern (116 to 85 kDa) associated with apoptosis in Hypocrellin A and B-treated cell lysates. In addition, caspase inhibition blocked the externalization of membrane PS, indicating that the loss of membrane phospholipid asymmetry is a downstream event of caspases activation. These results demonstrate that tumor cell death induced by Hypocrellin A and B is mediated by caspase proteases. In conclusion, this study identifies both Hypocrellins (A and B) as potent and promising photosensitizers for the treatment of NPC.

• Authors: S M Ali, M Olivo, G Y Yuen, S K Chee
• Journal: International journal of oncology (Int J Oncol) Vol. 19 Issue 3 Pg. 633-43 (Sep 2001) ISSN: 1019-6439 [Print] Greece
• PMID: 11494047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Caspase Inhibitors
• DNA, Neoplasm
• Enzyme Inhibitors
• Phosphatidylserines
• Photosensitizing Agents
• Poly(ADP-ribose) Polymerase Inhibitors
• Quinones
• Phenol
• Perylene
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• Caspase 3
• Caspases
• hypocrellin A
• hypocrellin B

Topics

• Annexin A5 (chemistry)
• Apoptosis
• Blotting, Western
• Caspase 3
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Differentiation (drug effects)
• DNA, Neoplasm (analysis)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Flow Cytometry
• Humans
• Nasopharyngeal Neoplasms (drug therapy, enzymology, genetics)
• Perylene (analogs & derivatives, therapeutic use)
• Phenol
• Phosphatidylserines (metabolism)
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (metabolism)
• Quinones (therapeutic use)
• Tumor Cells, Cultured (drug effects, enzymology)