Open Access

Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin

  • Authors:
    • Renata Sanovic
    • Barbara Krammer
    • Sandra Grumboeck
    • Thomas Verwanger
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/ijo_00000407
  • Pages: 921-939
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Abstract

Hypericin is used as a powerful naturally occurring photosensitizer in photodynamic therapy (PDT). Activated by visible light, it kills tumour cells and tissues via generation of reactive oxygen species (ROS). Depending on the protocol, apoptotic cell death can be achieved very effectively by hypericin-PDT. To analyze the fundamental molecular mechanisms leading to apoptosis induced by photodamage especially with regard to human skin cancer cells, we studied the alteration of the gene expression pattern in the human squamous cell carcinoma cell line A-431 at 1.5, 3, 5 and 8 h after hypericin-PDT by cDNA-macroarray technique. Radioactively labelled samples were hybridized onto macroarray filters containing PCR products of 9738 ESTs of the Incyte Human UniGEM Microarray clone set. In total, 168 genes were found to be differentially upregulated and 45 down-regulated. Verification of expression changes of 45 genes of interest was performed by quantitative real-time PCR. Due to the observed significant expression changes the following can be concluded: lipoprotein receptor-mediated endocytosis could play a role in the uptake of lipophilic hypericin. Extracellular signal transduction to the cell is reduced, cell detachment facilitated, changes of the morphology, cytoskeleton and formation of apoptotic bodies occur. The promotion of p38MAPK, ERK, JNK and Ras signalling pathways supports survival and/or apoptosis. Switches between life and death could be the strongly upregulated transcription factors c-jun and FOSB as well as the MAPK-phosphatase 1 DUSP-1, possibly activated via H3 histone modifications. ROS activate ER-stress pathways or adaptive response, and provoke damage protection against ROS, partly in a cell-type specific way.

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October 2009
Volume 35 Issue 4

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

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Spandidos Publications style
Sanovic R, Krammer B, Grumboeck S and Verwanger T: Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin. Int J Oncol 35: 921-939, 2009
APA
Sanovic, R., Krammer, B., Grumboeck, S., & Verwanger, T. (2009). Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin. International Journal of Oncology, 35, 921-939. https://doi.org/10.3892/ijo_00000407
MLA
Sanovic, R., Krammer, B., Grumboeck, S., Verwanger, T."Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin". International Journal of Oncology 35.4 (2009): 921-939.
Chicago
Sanovic, R., Krammer, B., Grumboeck, S., Verwanger, T."Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin". International Journal of Oncology 35, no. 4 (2009): 921-939. https://doi.org/10.3892/ijo_00000407