Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer cells

Bioorg Med Chem Lett. 2014 Apr 15;24(8):1884-8. doi: 10.1016/j.bmcl.2014.03.019. Epub 2014 Mar 18.

Abstract

Spiramine C-D, the atisine-type diterpenoid alkaloids isolated from the Chinese herbal medicine Spiraea japonica complex, are shown to have anti-inflammatory effects in vitro. In this study, we report that spiramine derivatives of spiramine C-D bearing α,β-unsaturated ketone induce apoptosis of Bax(-/-)/Bak(-/-) MEFs cell, which is positively corresponding their cytotoxicity of tumor cell lines including multidrug resistance MCF-7/ADR. The results indicated that oxazolidine ring is necessary, and derivatives bearing double 'Michael reaction acceptor' group would significantly increased activities both of inducing apoptosis of Bax(-/-)/Bak(-/-) cells and cytotoxicity of tumor cells. The result indicated that spiramine derivative with α,β-unsaturated ketone group is a new anti-cancer agent with a capability of inducing apoptosis of cancer cells in Bax/Bak-independent manner.

Keywords: Apoptosis; Bax(−/−)/Bak(−/−) cells; Cytotoxicity; Spiramine derivative; α,β-Unsaturated ketone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Gene Deletion
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Spiraea / chemistry
  • bcl-2 Homologous Antagonist-Killer Protein / drug effects*
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2-Associated X Protein / drug effects*
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds, 4 or More Rings
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • spiramine C
  • spiramine D