Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells

Anticancer Res. 2014 Nov;34(11):6473-80.

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.

Materials and 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.

Conclusion: Osthole could be considered as a potential compound for cancer therapy and chemoprevention.

Keywords: Osthole; RK33; TE671 cells; apoptosis; cell cycle; high-performance counter-current chromatography; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Calcium Channel Blockers / pharmacology
  • Cell Cycle / drug effects*
  • Cell Proliferation / drug effects*
  • Cerebellar Neoplasms / drug therapy
  • Cerebellar Neoplasms / metabolism
  • Cerebellar Neoplasms / pathology*
  • Coumarins / pharmacology*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Flow Cytometry
  • Humans
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology*
  • Medulloblastoma / drug therapy
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • CDKN1A protein, human
  • Calcium Channel Blockers
  • Coumarins
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • osthol