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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2013

Open Access 01-12-2013 | Short report

Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice

Authors: Xiuli Bi, Nicole Pohl, Huali Dong, Wancai Yang

Published in: Journal of Hematology & Oncology | Issue 1/2013

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Abstract

Background

Both selenium and non-steroidal anti-inflammatory drug (NSAID) sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms.

Results

We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p<0.01). Mechanistic studies revealed that the combination of selenium and sulindac led to the significant induction of the expression of p27 and p53 and JNK1 phosphorylation, and led to the suppression of β-catenin and its downstream targets. Impressively, the data also showed that demythelation on p21 promoter was associated with tumor inhibition by the combination of selenium and sulindac.

Conclusions

The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.
Appendix
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Metadata
Title
Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice
Authors
Xiuli Bi
Nicole Pohl
Huali Dong
Wancai Yang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2013
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-6-8

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