title: Flavonoids from Orostachys japonicus A. Berger inhibit the invasion of LnCaP prostate carcinoma cells by inactivating Akt and modulating tight junctions.
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.
authors.affiliation: Dongnam Institute of Radiological & Medicine Sciences, Busan 619-953, Korea. lwshmo@gshp.gsnu.ac.kr.
authors.forename: Dong Yeok
authors.initials: DY
authors.lastname: Shin
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Jung
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Soon Chan
authors.initials: SC
authors.lastname: Hong
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D029627:Crassulaceae / Q000737:chemistry*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D051058:Oncogene Protein v-akt
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