Diarylheptanoids derived from Alpinia officinarum induce apoptosis, S-phase arrest and differentiation in human neuroblastoma cells.
Anticancer Res
; 29(12): 4981-8, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-20044605
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 ANDMETHODS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Divisão Celular
/
Fase S
/
Apoptose
/
Alpinia
/
Diarileptanoides
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão