title: CXCR4 and PTEN are involved in the anti-metastatic regulation of anethole in DU145 prostate cancer cells.
abstract: Anethole has been known to have chemopreventive activities as a suppressor of the incidence and multiplicity of both invasive and noninvasive carcinomas. The goal of this study was to understand the anti-metastatic effect of anethole through C-X-C chemokine receptor type 4 (CXCR4)/tumor suppressor phosphatase and tensin homologue (PTEN) axis in DU145 prostate cancer cells. Anethole reduced both of the RNA level and the protein level of CXCR4 in a dose-dependent manner without cytotoxicity. Anethole also reduced the expression of CXCR4 and prolonged the expression of PTEN in DU145 prostate cancers. The phosphorylation of AKT and phosphatidylinositol-3kinase (PI3K) were decreased with anethole. The inhibition metastatic effect of anethole was arisen from down-regulating CXCR4 and up-regulating PTEN. Morphologically, anethole significantly inhibited the invasion of DU145 cell and down-regulated the activities of matrix-metalloproteinase (MMPs) in a dose-dependent manner. However, anethole didnot decrease the phosphorylation of PI3K and AKT while PTEN was silenced. Furthermore, the CXCR4 inhibition of anethole was not caused to proteasomal or lysosomal of CXCR4. Taken together, anethole demonstrated to act as the CXCR4 antagonist and as the PTEN activator which resulted to PI3K/AKT-mediated inhibition of the metastatic prostate cancer progressions.
authors: Beckman Laser Institute Korea, Dankook University, 119 Dandae-ro, Cheonan, Chungnam 330-714, Republic of Korea.
authors: Yun-Hee
authors: YH
authors: Rhee
authors: Beckman Laser Institute Korea, Dankook University, 119 Dandae-ro, Cheonan, Chungnam 330-714, Republic of Korea; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, 119 Dandae-ro, Cheonan, Chungnam 330-714, Republic of Korea.
authors: Phil-Sang
authors: PS
authors: Chung
authors: College of Oriental Medicine, Kyunghee University, Seoul 130-701, Republic of Korea.
authors: Sung-Hoon
authors: SH
authors: Kim
authors: Beckman Laser Institute Korea, Dankook University, 119 Dandae-ro, Cheonan, Chungnam 330-714, Republic of Korea; Department of Biomedical Engineering, College of Medicine, Dankook University, 119 Dandae-ro, Cheonan, Chungnam 330-714, Republic of Korea; Biomedical Translational Research Institute, Dankook University, 119 Dandae-ro, Cheonan, Chungnam 330-714, Republic of Korea. Electronic address: jcahn@dankook.ac.kr.
authors: Jin Chul
authors: JC
authors: Ahn
mesh_terms: D000081248:Allylbenzene Derivatives; D000840:Anisoles / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D016588:Anticarcinogenic Agents; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C527276:CXCR4 protein, human; C494929:PTEN protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human; C006578:anethole
keywords: Anethole; CXCR4; Metastasis; PTEN; Prostate cancer