Ferrearin C induces apoptosis via heme oxygenase-1 (HO-1) induction in neuroblastoma

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 fibrob...

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Bibliographic Details
Published in:Journal of natural medicines 2011-07, Vol.65 (3-4), p.431-439
Main Authors: Hayama, Tatsuya, Tabata, Keiichi, Uchiyama, Taketo, Fujimoto, Yasuo, Suzuki, Takashi
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cell Line
Cell Line, Tumor
Complementary & Alternative Medicine
Flow Cytometry
Heme Oxygenase-1 - genetics
Heme Oxygenase-1 - metabolism
Humans
Inhibitor of Apoptosis Proteins - genetics
Inhibitor of Apoptosis Proteins - metabolism
Lignans - chemistry
Lignans - pharmacology
Medicinal Chemistry
Models, Biological
Molecular Structure
Neuroblastoma - metabolism
Original Paper
Pharmacology/Toxicology
Pharmacy
Plant Sciences
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Summary: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.
ISSN:1340-3443
1861-0293
DOI:10.1007/s11418-011-0514-1