Growth inhibition and apoptosis induction by alternol in pancreatic carcinoma cells

World J Gastroenterol. 2015 Apr 21;21(15):4526-35. doi: 10.3748/wjg.v21.i15.4526.

Abstract

Aim: To investigate the effect of alternol on pancreatic cancer cells.

Methods: Pancreatic cancer cells PANC-1 and BxPC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a TdT-mediated dUTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting.

Results: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and BxPC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner.

Conclusion: Our results suggested that alternol is a candidate for treatment of pancreatic cancer.

Keywords: Alternol; Apoptosis; Cell cycle; Chemotherapy; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dose-Response Relationship, Drug
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • S Phase Cell Cycle Checkpoints / drug effects
  • Signal Transduction / drug effects
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Alternol
  • Antineoplastic Agents
  • BCL2 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Heterocyclic Compounds, 4 or More Rings
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • CASP3 protein, human
  • Caspase 3