Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT

Malini Olivo, Mohamed Ali-Seyed

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is a promising treatment that is approved by the US FDA for the treatment of oesophageal and lung cancer as well as for age-related macular degeneration. In this study, using standard tissue culture techniques, the photo cytotoxicity and apoptotic mechanisms of Calphostin C (Cal C), a perylenequinone microbial compound in combination with visible light dose was examined in different tumor cell lines. Our results demonstrated both a time and drug-light dose dependence in Cal-C-PDT induced photo toxicity and apoptotic cell death. The induction of apoptosis by Cal C-PDT was found to transit to necrotic cell death at higher drug and light doses. The detection of apoptosis in irradiated tumor cells was performed using various approaches including cell morphology analysis, flow cytometry [DNA fragmentation and phosphatidylserine (PS) externalization] and biochemical assays (activation of caspases). Time-course analysis of Cal C cellular uptake and distribution showed a rapid increase within the cellular compartments. The activation of caspases and nuclear fragmentation was evidenced at a maximum time point of 3 h after irradiation. By the use of specific caspase substrates, significant activation of caspase-8 and -3 was found. Mitochondrial involvement during Cal C-PDT-induced apoptosis was proven by a rapid reduction of the mitochondrial membrane potential. Furthermore, Cal C-PDT also enhanced FasL expression, which then induced Fas signalling-dependent cell death in NPC and colon cancer cell lines tested. Our results contribute to a deeper understanding of the processes involved in apoptotic cell death following photodynamic treatment with Cal C.

Original languageEnglish
Pages (from-to)537-548
Number of pages12
JournalInternational Journal of Oncology
Volume30
Issue number3
Publication statusPublished - Mar 2007
Externally publishedYes

Fingerprint

Photochemotherapy
Apoptosis
Cell Death
Caspases
Neoplasms
Light
Tissue Culture Techniques
Caspase 8
Mitochondrial Membrane Potential
Phosphatidylserines
Macular Degeneration
DNA Fragmentation
Esophageal Neoplasms
Tumor Cell Line
Caspase 3
Pharmaceutical Preparations
Colonic Neoplasms
Lung Neoplasms
Flow Cytometry
Therapeutics

Keywords

  • Apoptosis
  • Calphostin C
  • Caspases nasopharyngeal carcinoma
  • Photodynamic therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT. / Olivo, Malini; Ali-Seyed, Mohamed.

In: International Journal of Oncology, Vol. 30, No. 3, 03.2007, p. 537-548.

Research output: Contribution to journalArticle

Olivo, Malini ; Ali-Seyed, Mohamed. / Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT. In: International Journal of Oncology. 2007 ; Vol. 30, No. 3. pp. 537-548.
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