title: Osthole inhibits the tumorigenesis of hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer, and the majority of patients with HCC are deprived of effective curative methods. Osthole is a Chinese herbal medicine which has been reported to possess various pharmacological functions, including hepatocellular protection. In the present study, we investigated the anticancer activity of osthole using HCC cell lines. We found that osthole inhibited HCC cell proliferation, induced cell cycle arrest, triggered DNA damage and suppressed migration in HCC cell lines. Furthermore, we demonstrated that osthole not only contributed to cell cycle G2/M phase arrest via downregulation of Cdc2 and cyclin B1 levels, but also induced DNA damage via an increase in ERCC1 expression. In addition, osthole inhibited the migration of HCC cell lines by significantly downregulating MMP-2 and MMP-9 levels. Finally, we demonstrated that osthole inhibited epithelial-mesenchymal transition (EMT) via increasing the expression of epithelial biomarkers E-cadherin and β-catenin, and significantly decreasing mesenchymal N-cadherin and vimentin protein expression. These results suggest that osthole may have potential chemotherapeutic activity against HCC.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhi-Kun
authors.initials: ZK
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Tan
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Luo
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhong-Yu
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003374:Coumarins / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: D002121:Calcium Channel Blockers; D003374:Coumarins; C046627:osthol