Curcumin decreases cell proliferation rates through BTG2-mediated cyclin D1 down-regulation in U937 cells.
Curcumin is a promising chemopreventive agent due to its multiple properties including anti-inflammation, induction of apoptosis and inhibition of signal cascades involving cell proliferation. It has been reported that curcumin-treated cells show decreased expression of cyclin D1, ultimately resulting in decreased cell growth rate. Thus, modulation of cell cycle regulatory proteins by curcumin has been suggested as one of the important mechanisms underlying its chemopreventive effects. However, the precise molecular mechanisms involving down-regulation of cyclin D1 by curcumin are not largely understood. In this study we investigated the mechanisms of cyclin D1 down-regulation by curcumin in U937 cells. Expressions of cyclin D1, particularly at protein and mRNA levels, were clearly decreased in curcumin-treated cells. The stability of cyclin D1 mRNA was not affected by curcumin treatment. Treatment of curcumin increased expression of BTG2 mRNA, a member of anti-proliferative gene family and a negative transcriptional regulator of cyclin D1. Furthermore, overexpression of BTG2 led to down-regulation of cyclin D1 mRNA expression in U937 cells. Nuclear translocation of p65 NF-kappaB is involved in the expression of cyclin D1 mRNA. Treatment of curcumin inhibited nuclear translocation of p65 NF-kappaB. Moreover, the expression of cyclin D1 mRNA was dramatically decreased after co-treatment curcumin with NF-kappaB inhibitors. The data presented here indicate that curcumin-induced down-regulation of cyclin D1 mRNA is mediated by induction of BTG2 as well as inhibition of nuclear translocation of NF-kappaB.
Kwon
Young-Kyu
YK
Department of Oriental Medicine, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Korea.
Jun
Ji-Man
JM
Shin
Sang-Woo
SW
Cho
Jae-We
JW
Suh
Seong-Il
SI
D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins; D020298:U937 Cells
D017874:Immediate-Early Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; C070114:BTG2 protein, human; D003513:Cycloheximide; D003474:Curcumin