Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells.

Abstract

Silibinin is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) and is reported to exhibit anticancer properties. Recently, it has been reported that silibinin inhibits hypoxia-inducible factor-1alpha (HIF-1alpha) expression in cancer cells. However, the precise mechanism by which silibinin decreases HIF-1 expression is not fully understood. In this study, silibinin inhibited basal and hypoxia induced expression levels of HIF-1alpha protein in LNCaP and PC-3 prostate cancer cells, while the rate of HIF-1alpha protein degradation and mRNA levels were not affected. We found that the decrease in HIF-1 protein by silibinin correlated with suppression of de novo synthesis of HIF-1alpha protein. Silibinin inhibited global protein synthesis coincided with reduction of eIF4F complex formation and induction of phosphorylation of the translation initiation factor 2alpha (eIF-2alpha) which can cause inhibition of general protein synthesis. These results suggest that silibinin's activity to inhibit HIF-1alpha protein expression is associated with the suppression of global protein translation.

• Authors: Hui-Jung Jung, Jong-Wook Park, Jason S Lee, Seong-Ryong Lee, Byeong-Churl Jang, Seong-Il Suh, Min-Ho Suh, Won-Ki Baek
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 390 Issue 1 Pg. 71-6 (Dec 04 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19778521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Protein Synthesis Inhibitors
• Silymarin
• Silybin

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, biosynthesis)
• Male
• Prostatic Neoplasms (metabolism)
• Protein Biosynthesis (drug effects)
• Protein Synthesis Inhibitors (pharmacology)
• Silybin
• Silymarin (pharmacology)