title: Anti-tumor effects of osthole on ovarian cancer cells in vitro.
abstract: BACKGROUND
  Cnidium monnieri (L.) Cusson is a commonly used traditional Chinese medicine to treat gynecological disease in some countries. Osthole, an active O-methylated coumadin isolated from Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-seizure and anti-inflammatory effects. However, the anti-tumor mechanism of osthole is not well known.
  
  
  OBJECTIVE
  Here, we show that osthole inhibited the proliferation and migration of two widely used ovarian cancer cell lines, A2780 and OV2008 cells, in a dose-dependent manner. The study investigated the molecular mechanisms underlying ovarian cancer cells proliferation, apoptosis, cell cycle arrest and migration triggered by osthole.
  
  
  METHODS
  Ovarian cancer cell lines A2780, OV2008 and normal ovarian cell line IOSE80 were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry assays were performed to confirm apoptosis and cell cycle. We employed wound healing and transwell assays to delineate invasive and migratory potential triggered by osthole.
  
  
  RESULTS
  MTT assays indicated that cell viability significantly decreased in ovarian cancer cells treated with osthole without effect on normal ovarian cells. Flow cytometric analysis revealed that osthole suppressed cells proliferation by promoting G2/M arrest and inducing apoptosis. The underlying mechanisms involved were regulation of the relative apoptotic protein Bcl-2, Bax and Caspase 3/9. In addition, wound healing and transwell assays revealed that the migratory potential and activity of matrix metalloproteinase MMP-2 and MMP-9 were markedly inhibited when cells were exposed to osthole.
  
  
  CONCLUSIONS
  Our findings suggested that osthole has the potential to be used in novel anti-cancer therapeutic formulations for ovarian cancer treatment.
authors: Department of Biotechnology, Dalian Medical University, Dalian 116044 Liaoning, China.
authors: Guoqiang
authors: G
authors: Jiang
authors: Department of Biotechnology, Dalian Medical University, Dalian 116044 Liaoning, China.
authors: Jia
authors: J
authors: Liu
authors: Department of Biotechnology, Dalian Medical University, Dalian 116044 Liaoning, China.
authors: Baoyin
authors: B
authors: Ren
authors: Department of Immunology, College of Basic Medical Science, Dalian Medical University, Lvshun south Road, Dalian 116044 Liaoning, China.
authors: Yawei
authors: Y
authors: Tang
authors: Department of Integrative Medicine, Dalian Medical University, Dalian 116044 Liaoning, China; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
authors: Lawrence
authors: L
authors: Owusu
authors: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors: Man
authors: M
authors: Li
authors: Department of Biotechnology, Dalian Medical University, Dalian 116044 Liaoning, China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Biotechnology, Dalian Medical University, Dalian 116044 Liaoning, China.
authors: Likun
authors: L
authors: Liu
authors: Department of Biotechnology, Dalian Medical University, Dalian 116044 Liaoning, China. Electronic address: liweiling2015@163.com.
authors: Weiling
authors: W
authors: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D056744:Cyclin B1 / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000473:pathology*; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D056744:Cyclin B1; D011480:Protease Inhibitors; D016203:CDC2 Protein Kinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C046627:osthol
keywords: Anti-tumor effect; Apoptosis; Bu2cAMP (PubChem CID: 64965); Crystal violet (PubChem CID: 11057); DAPI dihydrochloride (PubChem CID: 160166); Dimethyl sulfoxide (PubChem CID:90059); Edultin (PubChem CID: 5317013 ); Imperatorin acid (PubChem CID: 11415344); Migration; Osthole; Osthole (PubChem CID: 10228); Ovarian cancer; PMSF (PubChem CID: 4784); Thiazolyl blue tetrazolium bromide (PubChem CID: 64965)