|
KMID : 0620920090410090678
|
|
Experimental & Molecular Medicine
2009 Volume.41 No. 9 p.678 ~ p.0
|
|
|
Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells
|
|
Kang Dong-Woo
Oh Deuk-Hee
Lee Ji-Young
Park Seon-Yang
Woo Tae-Min
Kim Mi-Kyoung
Park Mi-Hee
Jang Young-Hoon
Min Do-Sik
|
|
|
Abstract
|
|
|
|
In spite of the importance of phospholipase D (PLD) in cell proliferation and tumorigenesis, little is known about the molecules regulating PLD expression. Thus, identification of small molecules inhibiting PLD expression would be an important advance for PLDmediated physiology. We examined one such here, denoted “Triptolide”, which was identified in a chemical screen for inhibitors of PLD expression using cell assay system based on measurement of PLD promoter activity. Triptolide significantly suppressed the expression of both PLD1 and PLD2 with sub-μM potency in MDA-MB-231 breast cancer cells as analyzed by promoter assay and RT-PCR. Moreover, triptolide abolished the protein level of PLD in a time and dose-dependent manner. Triptolide-induced PLD1 downregulation was also observed in all the cancer cells examined, suggesting a general phenomenon detected in various cancer cells. Decrease of PLD expression by triptolide suppressed both basal and PMA-induced PLD activity. In addition, triptolide inhibited activation of NFκB which increased PLD1 expression. Ultimately, downregulation of PLD by triptolide inhibited proliferation of breast cancer cells. Taken together, we demonstrate that triptolide suppresses the expression of PLD via inhibition of NFκB activation and then decreases cell proliferation.
|
|
|
KEYWORD
|
|
|
breast neoplasms, cell proliferation, gene expression regulation, neoplastic, NF-κ B, phospholipase D, triptolide
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|