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

S. M. Ali, M. Olivo, G. Y. Yuen, S. K. Chee

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)633-643
Number of pages11
JournalInternational Journal of Oncology
Volume19
Issue number3
Publication statusPublished - Sep 2001
Externally publishedYes

Fingerprint

Apoptosis
Caspases
Cell Death
Photosensitizing Agents
Phosphatidylserines
Membranes
Phospholipids
Peptide Hydrolases
Hypericum
Cell Line
Neoplasms
Oncogenic Viruses
Poly(ADP-ribose) Polymerases
hypocrellin B
Nasopharyngeal carcinoma
hypocrellin A
Tumor Cell Line
Diploidy
Cell Size
Caspase 3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Photodynamic-induced apoptosis of human nasopharyngeal carcinoma cells using Hypocrellins. / Ali, S. M.; Olivo, M.; Yuen, G. Y.; Chee, S. K.

In: International Journal of Oncology, Vol. 19, No. 3, 09.2001, p. 633-643.

Research output: Contribution to journalArticle

Ali, S. M. ; Olivo, M. ; Yuen, G. Y. ; Chee, S. K. / Photodynamic-induced apoptosis of human nasopharyngeal carcinoma cells using Hypocrellins. In: International Journal of Oncology. 2001 ; Vol. 19, No. 3. pp. 633-643.
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