Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells.
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.
Jung
Hui-Jung
HJ
Chronic Disease Research Center, School of Medicine, Keimyung University, Daegu 700-712, Republic of Korea.
Park
Jong-Wook
JW
Lee
Jason S
JS
Lee
Seong-Ryong
SR
Jang
Byeong-Churl
BC
Suh
Seong-Il
SI
Suh
Min-Ho
MH
Baek
Won-Ki
WK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011500:Protein Synthesis Inhibitors; D012838:Silymarin; D000077385:Silybin