eIF4A

Silvestrol is a specific eIF4A-targeting translation inhibitor. Silvestrol exhibits significant cytotoxic activity against many human cancer cell lines, such as lung, prostate, and breast cancer with IC ₅₀ values ranging from 1 to 7 nM.
Silvestrol significantly reduces the number of LNCaP cell colonies. Silvestrol (30 nM, 120 nM) induces apoptosis in LNCaP cells, through the mitochondrial pathway. Apaf-1, Caspase-2, caspase-9, and caspase-10 are involved in Silvestrol-induced apoptosis but caspase-3 and 7 are not.
Silvestrol induces caspase-3 activation and apoptotic cell death in a time- and dose-dependent manner. Silvestrol-mediated cell death is attenuated in ATG7-null mouse embryonic fibroblasts (MEFs) lacking a functional autophagy protein.
Silvestrol (50 nM) exerts an immediate inhibitory effect and causes near-static cell index compared with the control cells. Silvestrol (6.25 nM) enhances proliferation more than the vehicle control-treated cells, whereas a higher concentration of Silvestrol (50 nM) can inhibit cell proliferation. Silvestrol and episilvestrol display synergistic effects in combination with CDDP.

Silvestrol (1.5 mg/kg, i.p.) does not adversely affect production of human IgG by xenografted B-lymphocytes in mice. Silvestrol significantly prolongs survival compared to vehicle. There is no such lymphocyte infiltration detected in the spleens of any of the Silvestrol-treated mice, and nor do these animals exhibit any other obvious signs of lymphoma upon necropsy.