title: Ginsenoside Rg3 Inhibits Constitutive Activation of NF-κB Signaling in Human Breast Cancer (MDA-MB-231) Cells: ERK and Akt as Potential Upstream Targets.
abstract: Ginsenoside Rg3, one of the major ingredients of heat-processed ginseng, has been reported to inhibit the growth of various cancer cells. We previously reported that Rg3 inhibited the proliferation and induced apoptosis of breast cancer (MDA-MB-231) cells. In the present study, we have explored the mechanism underlying the anti-proliferative and proapoptotic effects of Rg3 in MDA-MB-231 cells, which have constitutively activated NF-κB and the mutant form of p53. Rg3 inhibited DNA binding and transcriptional activity of NF-κB and these effects were attributable to its suppression of IKKβ activity, degradation of IκBα and subsequent nuclear translocation of the p65 subunit of NF-κB. Similarly, the constitutive activation of ERK and Akt through phosphorylation was gradually reduced in MDA-MB-231 cells treated with Rg3. The pharmacological inhibitors of these kinases both U0126 (MEK1/2 inhibitor) and LY294002 (PI3K inhibitor) abrogated the NF-κB DNA binding activity in MDA-MB-231 cells. In addition, Rg3 treatment lowered the levels of the mutant p53 in concentration- and time-dependent manners. Rg3 also increased the association between p53 and its negative regulator Mdm2 in MDA-MB-231 cells. These findings suggest that Rg3 induced apoptosis in MDA-MB-231 cells, which is mediated by blocking NF-κB signaling via inactivation of ERK and Akt as well as destabilization of mutant p53.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Bo-Min
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Jeong-Hill
authors.initials: JH
authors.lastname: Park
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
authors.affiliation: Department of Food and Nutrition, Sungshin Women's University, Seoul, Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Na
keywords: Apoptosis; Ginsenoside Rg3; NF-κB; p53