Perifosine inhibits mammalian target of rapamycin signaling through facilitating degradation of major components in the mTOR axis and induces autophagy.

ABSTRACT: Perifosine is an alkylphospholipid exhibiting antitumor activity as shown in both preclinical studies and clinical trials. This activity is partly associated with its ability to inhibit Akt activity. It has been shown that the mammalian target of rapamycin (mTOR) axis plays a critical role in regulation of cell proliferation and survival primarily through functioning both downstream and upstream of Akt. The current study reveals a novel mechanism by which perifosine inhibits Akt and the mTOR axis. In addition to inhibition of Akt, perifosine inhibited the assembly of both mTOR/raptor and mTOR/rictor complexes. Strikingly, perifosine reduced the levels of Akt and other major components including mTOR, raptor, rictor, 70-kDa ribosomal S6 kinase, and 4E-binding protein 1 in the mTOR axis by p

SUBMITTER: Fu L 

PROVIDER: S-EPMC2789206 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature