Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells.

Seyed Mohamed Ali, Soo Khee Chee, Gan Yik Yuen, Malini Olivo

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region with a 5-year survival level of approximately 65%. To explore the novel therapeutic strategies in the management of this disease, the potential effects of photodynamic therapy (PDT) in NPC cells were investigated. PDT, a new mode of treatment, is based on the combined use of light-absorbing compounds and light irradiation. Two human NPC cells such as, poorly differentiated (NPC/CNE2) and moderately differentiated (NPC/TW0-1) and other types of tumor cells like colon (CCL-220.1) and bladder (SD) undergo rapid apoptosis when treated with PDT sensitized with hypericin (HY). It has been shown that this compound has a strong photodynamic effect on tumors and viruses. However, the initiating events of PDT sensitized HY-induced apoptosis are not identified completely. In this study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HY-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. Photosensitization of HY 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 irradiation and appeared to be a principal event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm within 2-3 h post PDT is a secondary event following the activation of initiator caspase-8 preceding Apaf-1, caspase-9 and caspase-3 activation, cleavage of PARP and DNA fragmentation.

Original languageEnglish
Pages (from-to)601-616
Number of pages16
JournalInternational Journal of Molecular Medicine
Volume9
Issue number6
Publication statusPublished - Jun 2002
Externally publishedYes

Fingerprint

Death Domain Receptors
Photochemotherapy
Apoptosis
Neoplasms
Caspase 3
Fas Ligand Protein
Caspase 8
Cytochromes c
Light
Initiator Caspases
Photosensitivity Disorders
Oncogenic Viruses
hypericin
Caspase 9
DNA Fragmentation
Disease Management
Tumor Cell Line
Membrane Potentials
Colon
Cytoplasm

ASJC Scopus subject areas

  • Genetics

Cite this

Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells. / Ali, Seyed Mohamed; Chee, Soo Khee; Yuen, Gan Yik; Olivo, Malini.

In: International Journal of Molecular Medicine, Vol. 9, No. 6, 06.2002, p. 601-616.

Research output: Contribution to journalArticle

Ali, Seyed Mohamed ; Chee, Soo Khee ; Yuen, Gan Yik ; Olivo, Malini. / Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells. In: International Journal of Molecular Medicine. 2002 ; Vol. 9, No. 6. pp. 601-616.
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