Positive Health Online

Abstract

LIU and COLLEAGUES, Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA researched at the molecular level, the inhibition of prostate cancer by selenium.

Background

A previous prevention trial showed that selenium supplementation was effective in reducing (by 50%) the incidence of prostate cancer.

Methodology

Selenium has been reported to inhibit the growth of prostate cancer cells in vitro. Multiple mechanisms are likely to be operative in the underlying effect of selenium.

Results

The authors report that Kruppel-like factor 4 (KLF4), a transcription factor of the KLF family, is an important target of selenium. We found that selenium up-regulates KLF4 expression and increases the DNA-binding activity of KLF4 in both the androgen-dependent LNCaP and the androgen-independent PC-3 human prostate cancer cells. The increase of KLF4 mRNA is accounted for primarily by enhanced transcription, although the contribution of a slight abatement in mRNA degradation cannot be ruled out. KLF4 knockdown using short interference RNA significantly weakens the effects of selenium on DNA synthesis inhibition, apoptosis induction, and the expression of three KLF4 target genes, cyclin D1, p21/WAF1, and p27/Kip1. In addition, the overexpression of KLF4 not only leads to an induction of apoptosis in the control cells, but also enhances the DNA synthesis-suppressive and-proapoptotic activities of selenium.

Conclusion

Taken together, the authors' results suggest that KLF4 plays a key role in mediating the growth-inhibitory effect of selenium in prostate cancer cells.

References

Liu S, Zhang H,  Zhu L,  Zhao L and  Dong Y. Kruppel-like factor 4 is a novel mediator of selenium in growth inhibition.  Molecular Cancer Research: MCR  6(2): 306-13, Feb 2008. NLM. NIHMS44832; NLM. PMC2366107