Oxymatrine induces human pancreatic cancer PANC-1 cells apoptosis via regulating expression of Bcl-2 and IAP families, and releasing of cytochrome c

J Exp Clin Cancer Res. 2011 Jun 29;30(1):66. doi: 10.1186/1756-9966-30-66.

Abstract

Background: Oxymatrine, an isolated extract from traditional Chinese herb Sophora Flavescens Ait, has been traditionally used for therapy of anti-hepatitis B virus, anti-inflammation and anti-anaphylaxis. The present study was to investigate the anti-cancer effect of oxymatrine on human pancreatic cancer PANC-1 cells, and its possible molecular mechanism.

Methods: The effect of oxymatrine on the viability and apoptosis was examined by methyl thiazolyl tetrazolium and flow cytometry analysis. The expression of Bax, Bcl-2, Bcl-x (L/S), Bid, Bad, HIAP-1, HIAP-2, XIAP, NAIP, Livin and Survivin genes was accessed by RT-PCR. The levels of cytochrome c and caspase 3 protein were assessed by Western blotting.

Results: Oxymatrine inhibited cell viability and induced apoptosis of PANC-1 cells in a time- and dose-dependent manner. This was accompanied by down-regulated expression of Livin and Survivin genes while the Bax/Bcl-2 ratio was upregulated. Furthermore, oxymatrine treatment led to the release of cytochrome c and activation of caspase-3 proteins.

Conclusion: Oxymatrine can induce apoptotic cell death of human pancreatic cancer, which might be attributed to the regulation of Bcl-2 and IAP families, release of mitochondrial cytochrome c and activation of caspase-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cytochromes c / biosynthesis*
  • Cytochromes c / genetics
  • Dose-Response Relationship, Drug
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Inhibitor of Apoptosis Proteins / genetics
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Quinolizines / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Quinolizines
  • RNA, Messenger
  • oxymatrine
  • Cytochromes c
  • Caspase 3