Inhibition of proliferation and induction of apoptosis by gamma-tocotrienol in human colon carcinoma HT-29 cells.
Nutrition
; 25(5): 555-66, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19121919
ABSTRACT
OBJECTIVE:
gamma-Tocotrienol is a major component of the tocotrienol-rich fraction of palm oil, but there is limited evidence that it has antitumor activity. In particular, the effects of gamma-tocotrienol on human colon carcinoma cells have not been reported. To investigate the chemopreventive effects of gamma-tocotrienol on colon cancer, we examined its capacity to inhibit proliferation and induce apoptosis in HT-29 cells and explored the mechanism underlying these effects.METHODS:
We cultured HT-29 cells in the presence of gamma-tocotrienol. The effect of gamma-tocotrienol on cell proliferation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, mitotic index, and colony formation. The cell-cycle distribution was investigated by flow cytometry. We measured apoptosis by nuclear staining, transmission electron microscopy, and DNA fragmentation. Apoptosis-related proteins and the nuclear factor-kappaB p65 protein were determined by western blotting and immunofluorescence.RESULTS:
gamma-Tocotrienol inhibited cell growth and arrested HT-29 cells in G(0)/G(1) phase. The 50% inhibitory concentration was 31.7 micromol/L (48 h). gamma-Tocotrienol-induced apoptosis in HT-29 cells was accompanied by downregulation of Bcl-2, upregulation of Bax, and activation of caspase-3. Furthermore, we found that gamma-tocotrienol reduced the expression level of total nuclear factor-kappaB p65 protein and inhibited its nuclear translocation.CONCLUSION:
The results indicated that gamma-tocotrienol inhibits cell proliferation and induces apoptosis in HT-29 cells in a time- and dose-dependent manner, and that this process is accompanied by cell-cycle arrest at G(0)/G(1), an increased Bax/Bcl-2 ratio, and activation of caspase-3. Our data also indicated that nuclear factor-kappaB p65 protein may be involved in these effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina E
/
Cromanos
/
Apoptose
/
Proliferação de Células
/
Fator de Transcrição RelA
Limite:
Humans
Idioma:
En
Revista:
Nutrition
Assunto da revista:
CIENCIAS DA NUTRICAO
Ano de publicação:
2009
Tipo de documento:
Article