RRC ID 37838
Author Tabata K, Yamazaki Y, Okada M, Fukumura K, Shimada A, Sun Y, Yasukawa K, Suzuki T.
Title Diarylheptanoids derived from Alpinia officinarum induce apoptosis, S-phase arrest and differentiation in human neuroblastoma cells.
Journal Anticancer Res
Abstract BACKGROUND:We have previously screened many natural products for their cytotoxic effects on neuroblastoma cell lines, and two diarylheptanoids derived from Alpinia officinarum, 7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one (Compound 1) and (5R)-5-methoxy-7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-3-heptanone (Compound 2), were shown to have potent cytotoxicity. On this basis, a detailed study of the antitumor activities of these two diarylheptanoids in neuroblastoma cell lines was performed.
MATERIALS AND METHODS:Cytotoxicity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. To measure apoptosis, nuclear shrinkage was monitored by Hoechst 33342 staining, and activation of caspases 3 and 9 was monitored by Western blotting. Cell cycle status was evaluated by flow cytometry with propidium iodide staining. Differentiated cells were photographed and counted in a randomized fashion.
RESULTS:Both diarylheptanoids showed significant cytotoxicity against neuroblastoma cell lines (IMR-32, SK-N-SH, NB-39). The compounds induced nuclear shrinkage and fragmentation, and activated caspase-3 and caspase-9. Flow cytometric analysis revealed induction of S-phase cell cycle arrest concurrently with an increased sub-G(1) cell population. Moreover, a low concentration (10(-8) M) of Compound 1 induced significant neurite branching in the NB-39 cell line.
CONCLUSION:Diarylheptanoids derived from A. officinarum have marked activity against neuroblastoma cells, acting through multiple mechanisms. Our results suggest that the two compounds studied here may be useful for the treatment of patients with neuroblastoma.
Volume 29(12)
Pages 4981-8
Published 2009-12-1
PII 29/12/4981
PMID 20044605
MeSH Alpinia / chemistry* Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects* Blotting, Western Caspase 3 / metabolism Caspase 9 / metabolism Cell Differentiation / drug effects* Cell Division / drug effects* Cell Line, Tumor Diarylheptanoids / pharmacology* Flow Cytometry Humans Neuroblastoma / pathology S Phase / drug effects*
IF 1.994
Times Cited 28
WOS Category ONCOLOGY
Resource
Human and Animal Cells