Induction of apoptosis by Hypericin through activation of caspase-3 in human carcinoma cells.

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

Research output: Contribution to journalArticle

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Abstract

Potent photosensitizer Hypericin (HY), is a lipid soluble perylquinone derivative of the genus Hypericum and has a strong photodynamic effect on tumors and viruses. However, the mechanisms of tumor cell death induced by this compound is still unclear. Furthermore, there are no reports on mechanisms in cell apoptosis induced by perylquinones in human nasopharyngeal carcinoma (NPC) and other mucosal cells. We studied the photodynamic effects of HY compound in poorly differentiated (CNE2) and moderately differentiated (TW0-1) human NPC cells as well as human mucosal colon (CCL-220.1) and bladder (SD) cells. Using these cell lines we investigated few hall marks of apoptotic commitments in a drug and light dose dependent manner. Tumor cells photoactivated with HY showed cell size shrinkage and an increase in the sub-diploid DNA content. A loss of membrane phospholipid asymmetry associated with apoptosis was induced in all tumor cell lines as evidenced by the externalization of phosphatidylserine. Under apoptotic conditions, Western blot analysis of poly (ADP-ribose) polymerase, a caspase substrate, showed the classical cleavage pattern (116-85 kDa) associated with apoptosis in PDT-treated cell lysates. In addition, 85 kDa cleaved product was blocked by using tetrapeptide caspase inhibitors such as DEVD-CHO or z-VAD-fmk. These results demonstrate that tumor cell death induced by photoactivated HY is mediated by caspase proteases. This study also identifies that CNE2, CCL-220.1 (colon) and SD (bladder) cell lines are more sensitive than TW0-1 cell line to PDT using perylquinone HY.

Original languageEnglish
Pages (from-to)521-530
Number of pages10
JournalInternational Journal of Molecular Medicine
Volume8
Issue number5
Publication statusPublished - Nov 2001
Externally publishedYes

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Caspase 3
Apoptosis
Carcinoma
Caspases
Cell Line
Colon
Urinary Bladder
Cell Death
Hypericum
Neoplasms
Oncogenic Viruses
Caspase Inhibitors
Photosensitizing Agents
Poly(ADP-ribose) Polymerases
Phosphatidylserines
Tumor Cell Line
Diploidy
Cell Size
hypericin
Phospholipids

ASJC Scopus subject areas

  • Genetics

Cite this

Induction of apoptosis by Hypericin through activation of caspase-3 in human carcinoma cells. / Ali, S. M.; Olivo, M.; Yuen, G. Y.; Chee, S. K.

In: International Journal of Molecular Medicine, Vol. 8, No. 5, 11.2001, p. 521-530.

Research output: Contribution to journalArticle

Ali, S. M. ; Olivo, M. ; Yuen, G. Y. ; Chee, S. K. / Induction of apoptosis by Hypericin through activation of caspase-3 in human carcinoma cells. In: International Journal of Molecular Medicine. 2001 ; Vol. 8, No. 5. pp. 521-530.
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