Volume 7 Supplement 2

13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)

Open Access

Lipid hydroperoxide, an intermediate product of oxidative stress, induces tumour progression-associated genes in hepatocarcinoma cells

  • Nataliya Rohr-Udilova1Email author,
  • Klaus Stolze2,
  • Bettina Grasl-Kraupp3,
  • Rolf Schulte-Hermann3 and
  • Markus Peck-Radosavljevic1
BMC Pharmacology20077(Suppl 2):A67

https://doi.org/10.1186/1471-2210-7-S2-A67

Published: 14 November 2007

Hepatocellular carcinoma often develops in the liver under chronic inflammation. Oxygen radicals, produced during inflammation, attack membrane lipids and form a number of oxidized metabolites including lipid hydroperoxides. The addition of linoleic acid hydroperoxide (LOOH) to the medium of recently established human hepatocarcinoma cell line (HCC-1.2) caused dose-dependent cell loss and enhanced LDH-release. Under subtoxic conditions LOOH induced intracellular hydrogen peroxide production and a decrease of cellular GSH content. Elevated expression of protooncogene c-myc and a catalytic subunit of telomerase hTERT were observed under LOOH exposure. Myc activation is sufficient to induce cell cycle entry in the absence of growth factors. Accordingly, the cells were pushed into the S- and G2/M-phase by LOOH. An increased expression of c-fos, c-jun, the antiapoptotic enzyme heme oxygenase 1 (HO-1) and the proinflammatory angiogenic interleukin-8 (IL-8) was detected under LOOH exposure. Pre-treatment of cells with antioxidant N-acetylcystein or with selenite, which induces the LOOH-detoxifying enzyme glutathione peroxidase, partially inhibited the expression of LOOH-induced genes implicating the involvement of oxidative stress. Application of SnPPIX, a HO-1 inhibitor, decreased the viability of HCC-1.2 cells indicating the protective role of HO-1 induction. These results show that lipid hydroperoxides may be an important driving force for carcinogenesis in the liver.

Authors’ Affiliations

(1)
Division of Hepatology and Gastroenterology, Department of Medicine III, Medical University of Vienna
(2)
Department of Natural Science, Veterinary University of Vienna
(3)
Institute of Cancer Research, Department of Medicine I, Medical University of Vienna

Copyright

© Rohr-Udilova et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

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