title: Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells.
abstract: BACKGROUND
  The aim of the present study was to determine the effects of osthole on cell proliferation and viability, cell-cycle progression and induction of apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell lines.
  
  
  METHODS
  Cell viability was measured by means of the MTT method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell-cycle progression was determined by flow cytometry, and induction of apoptosis by release of oligonucleosomes to the cytosol. The gene expression was estimated by a quantitative polymerase chain reaction (qPCR) method. High-performance counter-current chromatography (HPCCC) was applied for isolation of osthole from fruits of Mutellina purpurea.
  
  
  RESULTS
  Osthole decreased proliferation and cell viability of cancer cells in a dose-dependent manner. The tested compound induced apoptosis, increased the cell numbers in G1 and decreased cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A and TP53 gene expression depending on cancer cell type.
  
  
  CONCLUSIONS
  Osthole could be considered as a potential compound for cancer therapy and chemoprevention.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Jarząb
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland anetagrabarska@umlub.pl.
authors.forename: Aneta
authors.initials: A
authors.lastname: Grabarska
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Kiełbus
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Jeleniewicz
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dmoszyńska-Graniczka
authors.affiliation: Department of Pharmacognosy with Medical Plant Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Skalicka-Woźniak
authors.affiliation: Department of Pharmacognosy with Medical Plant Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Elwira
authors.initials: E
authors.lastname: Sieniawska
authors.affiliation: Department of Otolaryngology, MSWiA Hospital, Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Polberg
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland Department of Otolaryngology, MSWiA Hospital, Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stepulak
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003374:Coumarins / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008527:Medulloblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D002121:Calcium Channel Blockers; D003374:Coumarins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C046627:osthol
keywords: Osthole; RK33; TE671 cells; apoptosis; cell cycle; high-performance counter-current chromatography; proliferation