title: Regulation of crosstalk between epithelial to mesenchymal transition molecules and MMP-9 mediates the antimetastatic activity of anethole in DU145 prostate cancer cells.
abstract: The underlying antimetastatic mechanism of anethole (1) still remains unclear in association with the molecules of the epithelial to mesenchymal transition (EMT). Herein, the role of the EMT molecules was elucidated in terms of the antimetastatic activity of 1 using DU145 cells. Anethole significantly inhibited the adhesion of DU145 cells to vitronectin-coated plates, as well as migration in a wound-healing assay and invasion using a Boyden chamber. Also, anethole suppressed the expression of MMP-9 in DU145 cells by zymography, ELISA, and RT-PCR. Consistently, the silencing of MMP-9 enhanced the activity of 1 to upregulate the expression of E-cadherin and to attenuate the expression of Vimentin in DU145 cells. Compound 1 enhanced E-cadherin, which is an epithelial marker and attenuated the expression of Vimentin, Twist, and Snail as mesenchymal molecules at the mRNA level. Consistently, anethole upregulated E-cadherin and downregulated the expression of Vimentin, Twist and PI3K, and AKT at the protein level in DU145 cells. Conversely, the antimetastatic effects of 1 to inhibit invasion and the expression of MMP-9 and upregulate E-cadherin were reversed by the EMT inducer TGF-β in DU145 cells. Overall, the present findings suggest that anethole exerts antimetastatic activity via regulation of crosstalk between EMT molecules and MMP-9 on the basis of the in vitro data obtained.
authors: College of Korean Medicine, Kyung Hee University , Dongdaemun-gu, Seoul 131-701, Seoul, South Korea.
authors: ByungChul
authors: B
authors: Ha
authors: HyunSuk
authors: H
authors: Ko
authors: BongLee
authors: B
authors: Kim
authors: Eun Jung
authors: EJ
authors: Sohn
authors: Ji Hoon
authors: JH
authors: Jung
authors: Ji Sung
authors: JS
authors: Kim
authors: Jung Jae
authors: JJ
authors: Yoon
authors: Gunho
authors: G
authors: Won
authors: Ji-Hyun
authors: JH
authors: Kim
authors: Deok-beom
authors: DB
authors: Jung
authors: Miyong
authors: M
authors: Yun
authors: BumSang
authors: B
authors: Shim
authors: Sung-Hoon
authors: SH
authors: Kim
mesh_terms: D000081248:Allylbenzene Derivatives; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D051879:Twist-Related Protein 1 / Q000187:drug effects; D014746:Vimentin / Q000187:drug effects
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000970:Antineoplastic Agents; D015415:Biomarkers; D015820:Cadherins; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1; D014746:Vimentin; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9; C006578:anethole