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Flavonoids from Orostachys japonicus A. Berger Inhibit the Invasion of LnCaP Prostate Carcinoma Cells by Inactivating Akt and Modulating Tight Junctions

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Author(s): Dong Yeok Shin | Won Sup Lee | Ji Hyun Jung | Su Hyun Hong | Cheol Park | Hye Jung Kim | Gi-Young Kim | Hye Jin Hwang | Gon Sup Kim | Jin-Myung Jung | Chung Ho Ryu | Sung Chul Shin | Soon Chan Hong | Yung Hyun Choi

Journal: International Journal of Molecular Sciences
ISSN 1422-0067

Volume: 14;
Issue: 9;
Start page: 18407;
Date: 2013;
Original page

Keywords: Orostachys japonicus | flavonoids | LnCaP cells | tight junctions | Akt

ABSTRACT
Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins are frequently over-expressed in cancers and their overexpression is implicated in the invasive potential of cancer. Hence, we investigated the effects of flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ suppressed cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses cancer migration and invasion by tightening TJs through the suppression of claudin expression, and by suppressing MMPs in LnCaP human prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway.
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