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  • Original Paper
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Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization

Oncogene volume 20, pages 4070–4084 (2001)Cite this article

Abstract

Pyropheophorbide-a methylester (PPME) is a second generation of photosensitizers used in photodynamic therapy (PDT). We demonstrated that PPME photosensitization triggered apoptosis of colon cancer cells as measured by using several classical parameters such as DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c. Preincubation of cells with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protected against apoptosis mediated by PPME photosensitization showing that reactive oxygen species (ROS) are involved as second messengers. On the other hand, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (1O2) lifetime only increases necrosis without affecting apoptosis. Since PPME was localized in the endoplasmic reticulum (ER)/Golgi system and lysosomes, other messengers than ROS were tested such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c release from mitochondria. On the other hand, we demonstrated that the transduction pathways leading to NF-κB activation and apoptosis were clearly independent although NF-κB was shown to counteract apoptosis mediated by PPME photosensitization.

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Abbreviations

PDT:

photodynamic therapy

PPME:

pyropheophorbide-a methylester

FCS:

foetal calf serum

PARP:

poly (ADP-ribose) polymerase

DAPI:

4′,6-diamidine-2′-phenylindole dihydrochloride

TUNEL:

terminal deoxyuridine nick-end-labeling

ROS:

reactive oxygen species

1O2:

singlet oxygen

H2O2:

hydrogen peroxide

IL:

interleukin

TNF-α:

tumor necrosis factor α

ER:

endoplasmic reticulum

CSA:

cyclosporin A

PDTC:

pyrrolidine dithiocarbamate

NAC:

N-acetyl cysteine

D2O:

deuterium oxide, C-DCDHF-DA-AM, 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate di(acetoxymethyl ester)

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Acknowledgements

This work was supported by a grant from the Belgian National Fund for Scientific Research (NFSR) (Brussels, Belgium) and Télévie (Brussels, Belgium). J-Y Matroule is Research fellow from the FRIA and J Piette is Research Director from the NFSR (Brussels, Belgium).

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Authors and Affiliations

  1. Laboratory of Virology and Immunology, University of Liege, Liege, B-4000, Belgium

    Jean-Yves Matroule & Jacques Piette

  2. Laboratory of Human Histology, University of Liege, Liege, B-4000, Belgium

    Olivier Jolois

  3. QLT Inc., 887 Great Northern Way, Vancouver, BC, V5T 4T5, Canada

    Chris M Carthy, David J Granville & David W C Hunt

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  1. Jean-Yves Matroule
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Correspondence to Jacques Piette.

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Matroule, JY., Carthy, C., Granville, D. et al. Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization. Oncogene 20, 4070–4084 (2001). https://doi.org/10.1038/sj.onc.1204546

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