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

Kretzmann NA, Chiela E, Matte U, Marroni N, Marroni CA - Comp Hepatol (2012)

Bottom Line: 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: 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. nakfilho@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

NAC potentiates the effect of IFN by decreasing cell viability of HCC Huh7 cell line. Treatment with IFN or NAC, at 2.5x104 U/mL and 10 mM, respectively, significantly reduced cell viability after 48, 72, and 96 h of treatment. Treatment with NAC+IFN in the same doses significantly reduced cell viability after 24, 48, 72, and 96 h of treatment. Values are shown as means and standard errors of the mean (SEM). a-IFN x CO p<0.05. b- NAC x CO p<0.01. c- NAC+IFN x IFN p<0.05.
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Figure 2: NAC potentiates the effect of IFN by decreasing cell viability of HCC Huh7 cell line. Treatment with IFN or NAC, at 2.5x104 U/mL and 10 mM, respectively, significantly reduced cell viability after 48, 72, and 96 h of treatment. Treatment with NAC+IFN in the same doses significantly reduced cell viability after 24, 48, 72, and 96 h of treatment. Values are shown as means and standard errors of the mean (SEM). a-IFN x CO p<0.05. b- NAC x CO p<0.01. c- NAC+IFN x IFN p<0.05.

Mentions: The ideal doses of IFN-α (2.5 x 104) and NAC (10 mM) were found through dose curves using concentrations ranging from 0 to 105 IU/mL for IFN-α, and 5 to 20 mM for NAC (data not shown). Both drugs had a dose-dependent effect. IFN-α at a concentration of 2.5 x 104 U/mL (96 hours) decreased cell viability to about 30% in HepG2 and Huh7 cells, while 10 mM NAC reduced cell viability in both cell lines at 48, 72, and 96 hours. NAC and IFN-α combined have a more potent and earlier effect than any of these drugs alone, reducing cell viability to around 50% at 96 hours (Figures1 and2).


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

Kretzmann NA, Chiela E, Matte U, Marroni N, Marroni CA - Comp Hepatol (2012)

NAC potentiates the effect of IFN by decreasing cell viability of HCC Huh7 cell line. Treatment with IFN or NAC, at 2.5x104 U/mL and 10 mM, respectively, significantly reduced cell viability after 48, 72, and 96 h of treatment. Treatment with NAC+IFN in the same doses significantly reduced cell viability after 24, 48, 72, and 96 h of treatment. Values are shown as means and standard errors of the mean (SEM). a-IFN x CO p<0.05. b- NAC x CO p<0.01. c- NAC+IFN x IFN p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539937&req=5

Figure 2: NAC potentiates the effect of IFN by decreasing cell viability of HCC Huh7 cell line. Treatment with IFN or NAC, at 2.5x104 U/mL and 10 mM, respectively, significantly reduced cell viability after 48, 72, and 96 h of treatment. Treatment with NAC+IFN in the same doses significantly reduced cell viability after 24, 48, 72, and 96 h of treatment. Values are shown as means and standard errors of the mean (SEM). a-IFN x CO p<0.05. b- NAC x CO p<0.01. c- NAC+IFN x IFN p<0.05.
Mentions: The ideal doses of IFN-α (2.5 x 104) and NAC (10 mM) were found through dose curves using concentrations ranging from 0 to 105 IU/mL for IFN-α, and 5 to 20 mM for NAC (data not shown). Both drugs had a dose-dependent effect. IFN-α at a concentration of 2.5 x 104 U/mL (96 hours) decreased cell viability to about 30% in HepG2 and Huh7 cells, while 10 mM NAC reduced cell viability in both cell lines at 48, 72, and 96 hours. NAC and IFN-α combined have a more potent and earlier effect than any of these drugs alone, reducing cell viability to around 50% at 96 hours (Figures1 and2).

Bottom Line: 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: 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. nakfilho@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus