Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1/2 dependent way in human colorectal cancer cells.
Fitoterapia
; 101: 162-8, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25615593
ABSTRACT
Tanshinone I (TAN I) as one of the naturally occurring diterpenes from Salvia miltiorrhizae Bunge (Danshen) has been reported to exhibit an anti-cancer activity. However, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to elucidate the biological mechanism by which TAN I may induce the inhibition of cell growth in human colorectal cancer cells. The treatment of TAN I suppressed the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. However, the mRNA level of cyclin D1 did not changed by TAN I treatment. Inhibition of proteasomal degradation by MG132 blocked TAN I-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with TAN I. In addition, phosphorylation of cyclin D1 at threonine-286 was increased by TAN I and a point mutation of threonine-286 to alanine attenuated TAN I-mediated cyclin D1 downregulation. Inhibition of ERK1/2 suppressed cyclin D1 phosphorylation and subsequent downregulation by TAN I. From these results, we suggest that TAN I-mediated cyclin D1 downregulation may result from proteasomal degradation through its ERK1/2-mediated phosphorylation of threonine-286. In conclusion, the current study provides new mechanistic link between TAN I, cyclin D1 downregulation and cell growth in human colorectal cancer cells.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ciclina D1
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Sistema de Sinalização das MAP Quinases
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Abietanos
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Complexo de Endopeptidases do Proteassoma
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article