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Silvestrol inhibited protein synthesis in MDA-MB-231 breast and PC-3 prostate cancer cell lines with IC50 ~60 nM following a 1 h exposure) [1]. Silvestrol inhibited cell growth with an IC50 of 12.5-86 nM in four different HCC cell lines [3].
Silvestrol, a member of flavagline family of natural products from the genus of Aglaia exhibiting anti-cancer activity in vitro and in vivo and inhibiting translation initiation, was shown to be capable of modulating chemosensitivity in a mechanism-based mouse model.
Preclinical study: A previous study demonstrated that silvestrol showed antileukemia activity at nanomolar concentrations in both FLT3-wt overexpressing (THP-1) and FLT3-ITD (MV4-11) expressing AML cell lines (IC50 = 3.8 and 2.7 nM, respectively) and patients' primary blasts [IC50 = ~12 nM (FLT3-wt) and ~5 nM (FLT3-ITD)]. Moreover, silvestrol was observed to efficiently inhibite FLT3 translation resulting in a decrese of FLT3 protein expression by 80–90%. Animal study indicated that the median survival of silvestrol-treated mice significantly increased (silvestrol-treated vs vehicle-treated = 63 vs 29 days postengraftment) [2]. Another study showed that silvestrol could increase the activities of apoptosis and caspase 3/7. In vivo, the antitumor effect was found with 0.4 mg/kg silvestrol, and the survival of tumor-bearing mice was improved with a median survival time of 42 and 28 days in the silvestrol and control groups, respectively [3].
Clinical study: Currently, there is no clinical data about the anti-cancer efficacy of silvestrol. A grant application proposeed to pursue a Phase I clinical trial to assess the safety, maximum tolerated dose, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of silvestrol in patients with relapsed, refractory Chronic lymphocytic leukemia (Pre-Clinical and Clinical Development of Silvestrol in Chronic Lymphocytic).
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