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N-acetylcysteine improves antitumoural response of Interferon alpha by NF-kB downregulation in liver cancer cells

Nelson Alexandre Kretzmann12*, Eduardo Chiela3, Ursula Matte2, Norma Marroni2 and Claudio Augusto Marroni1

Author Affiliations

1 Post-Graduation Program in Medicine: Hepatology. Universidade Federal de Ciências da Saúde de Porto Alegre. Brazil. Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, CEP: 90050-170, Brazil

2 Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, CEP: 90035-903, Brazil

3 Pos-Graduated Program in Cell Biology, Universidade Federal do Rio Grande do Sul, Brazil, Porto Alegre, RS, CEP 91501-970, Brazil

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Comparative Hepatology 2012, 11:4  doi:10.1186/1476-5926-11-4

Published: 4 December 2012

Abstract

Background

Liver cancer is one of the most common malignancies in the world and at the moment, there is no drug intervention effective for the treatment of liver tumours. Investigate the effect of N-acetylcysteine (NAC), which has been studied for its antitumoural properties, on the toxicity of hepatocarcinoma (HCC) cells in vitro when used with the drug interferon alpha-2A (IFN), which is used clinically to treat HCC.

Results

NAC, IFN and NAC plus IFN reduced cell viability, as determined by MTT assay. More importantly, NAC potentiates the cytotoxic effect of IFN, with the best response achieved with 10 mM of NAC and 2.5 x 104 of IFN. These results were confirmed by Annexin/PI staining through flow cytometry and morphologic analyses. Co-treatment reduced the expression of the nuclear transcription factor kappa-B (NF-kB). In a similar way to NAC, RNAi against p65 potentiated the toxic effect of IFN, suggesting that, indeed, NAC may be enhancing the effect of IFN through inhibition of NF-kB.

Conclusions

Our results support the notion that NAC may be an important drug for the treatment of liver tumours as primary or adjuvant therapy. IFN has a limited clinical response, and therefore, the anti-proliferative properties of NAC in the liver should be explored further as an alternative for non-responders to IFN treatment.

Keywords:
N-acetylcysteine; Interferon alpha; NF-kB; Liver cancer cells