Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol.

ABSTRACT:

Background

Flavaglines are a family of natural products from the genus Aglaia that exhibit anti-cancer activity in vitro and in vivo and inhibit translation initiation. They have been shown to modulate the activity of eIF4A, the DEAD-box RNA helicase subunit of the eukaryotic initiation factor (eIF) 4F complex, a complex that stimulates ribosome recruitment during translation initiation. One flavagline, silvestrol, is capable of modulating chemosensitivity in a mechanism-based mouse model.

Methodology/principal findings

Among a number of flavagline family members tested herein, we find that silvestrol is the more potent translation inhibitor among these. We find that silvestrol impairs the ribosome recruitment step of translation initiation by affecting the composition of th

SUBMITTER: Cencic R 

PROVIDER: S-EPMC2671147 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature