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

  • Authors:
    • Malini Olivo
    • Mohamed Ali-Seyed
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/ijo.30.3.537
  • Pages: 537-548
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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.

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March 2007
Volume 30 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Olivo M and Olivo M: Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT. Int J Oncol 30: 537-548, 2007
APA
Olivo, M., & Olivo, M. (2007). Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT. International Journal of Oncology, 30, 537-548. https://doi.org/10.3892/ijo.30.3.537
MLA
Olivo, M., Ali-Seyed, M."Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT". International Journal of Oncology 30.3 (2007): 537-548.
Chicago
Olivo, M., Ali-Seyed, M."Apoptosis signalling mechanisms in human cancer cells induced by Calphostin-PDT". International Journal of Oncology 30, no. 3 (2007): 537-548. https://doi.org/10.3892/ijo.30.3.537