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p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative

Oncogene volume 27, pages 3010–3020 (2008)Cite this article

Abstract

In this study, we provide evidence that photostimulation of various cancer cells preloaded with a new photosensitizing compound, tetrakis-meso-(4-ethyleneglycol-2,3,5,6-tetrafluorophenyl) porphyrin (PORF-TEG), results in rapid activation of the cell death machinery. PORF-TEG, although primarily localized in lysosomes, induces mitochondria-driven apoptosis. The induction of apoptosis is accompanied by immediate and sustained activation of p38 mitogen-activated protein kinase (MAPK) and transient activation of c-Jun N-terminal kinase (JNK). Conversely, the inhibition of p38 by PD 169316 or SB202190 and by the p38α dominant-negative mutant as well as the deletion of the p38α gene (MEFs-KO) protected cells from apoptosis, whereas inhibition of JNK did not. Activation of the p38 signaling pathway occurs upstream of caspase activation. In addition, preincubation of cells with scavengers of reactive oxygen species attenuated p38 and caspase activation and increased cell survival, thus connecting reactive oxygen species formation with the activation of the p38 pathway. Later events included degradation of Bcl-2, activation of tBid, and cleavage of Bad and Mcl-1. The data suggest a key role for p38 MAPK in PORF-TEG-photoinduced apoptosis.

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Acknowledgements

This work was funded by grant awarded by the Ministry of Education of the Czech Republic LC06077 and further supported in part by project from the Grant Agency of the Czech Republic AV0Z50520514 and grant KAN200200651 awarded by Grant Agency of the Academy of Sciences of the Czech Republic. We thank Dr AR Nebreda EMBL researcher (CNIO-Spanish National Cancer Center, Madrid, Spain.) for providing MEFs wt and KO cells and Dr L Andera for critical reading and suggestions during preparation of this manuscript.

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  1. Department of Molecular Virology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    J Kralova, M Dvorak & M Koc

  2. Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Czech Republic

    V Kral

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  1. J Kralova
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Correspondence to J Kralova.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Kralova, J., Dvorak, M., Koc, M. et al. p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative. Oncogene 27, 3010–3020 (2008). https://doi.org/10.1038/sj.onc.1210960

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