Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells.
10.3858/emm.2009.41.9.074
- Author:
Dong Woo KANG
1
;
Ji Young LEE
;
Deuk hee OH
;
Seon Yang PARK
;
Tae Min WOO
;
Mi Kyoung KIM
;
Mi Hee PARK
;
Young Hoon JANG
;
Do Sik MIN
Author Information
1. Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735, Korea. minds@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
breast neoplasms;
cell proliferation;
gene expression regulation, neoplastic;
NF-kappaB;
phospholipase D;
triptolide
- MeSH:
Antineoplastic Agents, Alkylating/*pharmacology;
Breast Neoplasms/drug therapy/enzymology;
Cell Line, Tumor;
Cell Proliferation/drug effects;
Diterpenes/*pharmacology;
Epoxy Compounds/pharmacology;
Female;
Gene Expression Regulation, Neoplastic/*drug effects;
Humans;
NF-kappa B/genetics/metabolism;
Phenanthrenes/*pharmacology;
Phospholipase D/*genetics/metabolism
- From:Experimental & Molecular Medicine
2009;41(9):678-685
- CountryRepublic of Korea
- Language:English
-
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 PLD-mediated 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-microM 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 NFkappaB 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 NFkappaB activation and then decreases cell proliferation.
