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.
Chen Yan  1 ,  Li Huang  2 ,  Hong-Chun Liu  3 ,  Duo-Zhi Chen  4 ,  Hai-Yang Liu  4 ,  Xiao-Hui Li  4 ,  Yu Zhang  4 ,  Mei-Yu Geng  3 ,  Quan Chen  5 ,  Xiao-Jiang Hao  6
Affiliations
  • 1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China; The Key Laboratory of Chemistry for Natural Product of Guizhou Province, Chinese Academy of Science, Beijing 100101, PR China.
  • 2. The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, RP China.
  • 3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
  • 4. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China.
  • 5. The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, RP China. Electronic address: [email protected].
  • 6. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China. Electronic address: [email protected].
PMID: 24684844 DOI: 10.1016/j.bmcl.2014.03.019
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.