Tamoxifen enhancement of TNF-α induced MnSOD expression: Modulation of NF-κB dimerization

Chotiros Daosukho, Kelley Kiningham, Edward J. Kasarskis, Wanida Ittarat, Daret K. St. Clair

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Manganese superoxide dismutase (MnSOD) has been shown to suppress the development of cancer. Tamoxifen (TAM), a nonsteroidal anti-estrogen that is widely used in chemotherapy, is known to be a modulator of antioxidant status. However, the mechanism by which TAM mediates antioxidant enzyme induction remains unclear. In this study we investigated TAM enhancement of MnSOD induction by TNF-α. The results show that co-treatment with TAM and TNF-α increases the MnSOD promoter/enhancer driven luciferase activity, MnSOD mRNA and protein levels. Interestingly, co-treatment with TAM and TNF-α drastically decreases the binding activity of the p50/p50 homodimer and increases that of the p50/p65 heterodimer compared to TNF-α alone. This change in DNA binding could not be attributed to a decrease in the level of p50, its precursor, p105, or its inhibitors. Furthermore, TAM did not enhance degradation of IκB-α. These results suggest that p50/p50 homodimer may act as an inhibitory complex of MnSOD expression. Modulation of the DNA binding activity in favor of the p50/p65 complex may enhance NF-κB mediated induction of MnSOD by TAM. These findings reveal a potential novel mechanism for the induction of the human MnSOD gene.

Original languageEnglish
Pages (from-to)3603-3610
Number of pages8
Issue number22
StatePublished - 2002

Bibliographical note

Funding Information:
This work was supported by NIH grants CA 49797 and CA 59835, an Independent Research Career Award to DK St Clair (HL-03544) and a Royal Golden Jubilee Research Fellowship (The Thailand Research Fund) to C Daosukho.


  • MnSOD
  • NF-κB
  • Tamoxifen
  • Tumor control
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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