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

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.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.Hepatocarcinoma (HCC) is the most common primary malignancy of the liver, typically observed as a complication of chronic liver disease. It is the fifth most common tumour worldwide, with more than 700,000 new cases per year [1]. Cirrhosis of different etiologies such as alcohol, primary biliary cirrhosis, or chronic infection with hepatitis B or C (HBV, HCV) are risk factors that predispose patients to HCC [2]. The development of HCC is a complex process, with the accumulation of genetic and epigenetic alterations, which pass through the events of tumour initiation, promotion and progression [2-4].HCV chronic infection can induce chaotic cellular signalling, raising tumour cells with activation of epidermal growth factor (EGF) [5] and NF-kB, contributing to tumour development and survival of infected cells [6]. Interferon (IFN) is the most used drug in chronic hepatitis and HCC due to its properties of immune response activation and also regulation of differentiation and cell growth. IFN has also shown satisfactory results mainly in treating hematologic malignancies and Kaposi’s Sarcoma, a