2. Academic Validation
  3. Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer cells

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

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: chenq@ioz.ac.cn.
  • 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: haoxj@mail.kib.ac.cn.
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.

Figures