Spiramine derivatives induce apoptosis of Bax−/−/Bak−/− cell and cancer cells

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.