Silvestrol, a eukaryotic translation initiation factor 4A inhibitor, induces autophagy and caspase-mediated apoptosis.

Silvestrol shows significant cytotoxic activity against many human cancer cell lines, such as lung, prostate, and breast cancer (IC50: ranging from 1 to 7 nM). Silvestrol significantly reduces the number of LNCaP cell colonies. Silvestrol-mediated cell death is attenuated in ATG7-null mouse embryonic fibroblasts lacking a functional autophagy protein. Silvestrol induces caspase-3 activation and apoptotic cell death in a time- and dose-dependent manner. Silvestrol and episilvestrol show synergistic effects in combination with CDDP. Silvestrol (30 nM, 120 nM) induces apoptosis in LNCaP cells, through the mitochondrial pathway. 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 [1][2][3][4].

Silvestrol significantly prolongs survival compared to vehicle. Silvestrol (1.5 mg/kg, i.p.) does not adversely affect the production of human IgG by xenografted B-lymphocytes in mice [5].