Published in:
01-07-2011 | Original Paper
Ferrearin C induces apoptosis via heme oxygenase-1 (HO-1) induction in neuroblastoma
Authors:
Tatsuya Hayama, Keiichi Tabata, Taketo Uchiyama, Yasuo Fujimoto, Takashi Suzuki
Published in:
Journal of Natural Medicines
|
Issue 3-4/2011
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Abstract
We investigated the cytotoxicity of six neolignans (1–6), which are similar in structure to furanocyclohexenone with an angular allyl group, in human neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, SK-N-SH) and normal cells [human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)] using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Two neolignans, ferrearin C (1) and 2, showed significant cytotoxicity in neuroblastoma cells. Typical morphologic features of apoptosis were observed for the ferrearin-type neolignans using Hoechst 33342, and apoptotic cytoplasmic membrane inversion was also induced by ferrearin-type neolignans in IMR-32. Furthermore, a Proteome Profiler Array showed that the ferrearin-type neolignans induced the marked expression of heme oxygenase-1 (HO-1). In a western blot analysis, ferrearin C (1) increased the level of Bax and reduced the level of survivin, indicating the activation of the mitochondrial pathway of apoptosis.