1. Cell Cycle/DNA Damage
  2. Eukaryotic Initiation Factor (eIF)

Silvestrol (Synonyms: (-)-Silvestrol)

Cat. No.: HY-13251 Purity: 98.00%
Handling Instructions

Silvestrol is a eukaryotic translation initiation factor 4A (eIF4A) inhibitor isolated from the fruits and twigs of Aglaia foveolata.

For research use only. We do not sell to patients.

Silvestrol Chemical Structure

Silvestrol Chemical Structure

CAS No. : 697235-38-4

Size Price Stock Quantity
10 mM * 1 mL USD 5401 In-stock
Estimated Time of Arrival: December 31
1 mg USD 840 In-stock
Estimated Time of Arrival: December 31
2 mg USD 1500 In-stock
Estimated Time of Arrival: December 31
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Other Forms of Silvestrol:

    Silvestrol purchased from MCE. Usage Cited in: Nature. 2014 Sep 4;513(7516):65-70.

    Immunoblots of lysates from human T-ALL lines treated with Silvestrol (25 nM, 24h) and probed as indicated.

    Silvestrol purchased from MCE. Usage Cited in: Blood. 2014 Dec 11;124(25):3758-67.

    (A)Protein lysates from human splenic B cells are harvested 24 hours after treatment with Isotype + Vehicle, Isotype + 10 nM Silvestrol, anti-BCR + Vehicle, or anti-BCR + 10 nM Silvestrol and incubated with m7GTP Sepharose beads overnight at 4°C. Western blot analysis is used to observe eIF4A and eIF4E binding to m7GTP. Data are representative of 3e independent experiments. (B) Twenty-four hours after treatment, cells are incubated with 1 mCi L-[35S]methionine and L-[35S]cy

    Silvestrol purchased from MCE. Usage Cited in: Cancer Discov. 2015 Jul;5(7):768-81.

    Immunoblots of four colorectal cell lines upon treatment with increasing concentration of Silvestrol or solvent control (n=2).

    Silvestrol purchased from MCE. Usage Cited in: EMBO J. 2016 Jun 1;35(11):1186-203.

    The inhibitory effect of Silvestrol in translation is observed despite a two to five fold increase of reporter mRNA levels in HEK293 cells

    Silvestrol purchased from MCE. Usage Cited in: Antiviral Res. 2017 Jan;137:76-81.

    PIM1 levels are strongly decreased (to almost below detection limits) in the presence of 10 nM Silvestrol. This inhibitory effect persists for at least 5 days using a single dose of Silvestrol, without affecting cellular β-Actin levels.

    Silvestrol purchased from MCE. Usage Cited in: University of Maryland, Baltimore. Molecular Medicine. 2014.

    IgG positive B-cells display more significant modulation of CARD11 protein levels upon BCR activation and treatment with Silvestrol.

    Silvestrol purchased from MCE. Usage Cited in: Oncogene. 2017 Nov 9;36(45):6225-6234.

    Sin1 protein level decreases in cells treated with silvestrol. HT29-P or HCT116 cells were treated with indicated concentration of Silvestrol for 24 h. The ratio of Sin1/GAPDH and Snail/GAPDH in DMSO (0 nM Silvestrol) treated cells is designated as 1.0.

    Silvestrol purchased from MCE. Usage Cited in: Viruses. 2017 Dec 18;9(12). pii: E388.

    Western blotting analysis of A549 cell lysates obtained at the indicated times post-infection with the PR8 strain of IAV and treated with 320 nM silvestrol (Sil.) or 20 nM pateamine A (PatA) at 4 hpi or the equivalent time after mock infection.

    Silvestrol purchased from MCE. Usage Cited in: Antiviral Res. 2017 Dec 16;150:123-129.

    Huh-7 cells are infected with HCoV-229E at an MOI of 3 and treated with the indicated concentrations of silvestrol. Cell lysates are prepared at 12 h p.i. and 48 h p.i. as indicated and the accumulation of viral N and nsp8 proteins is determined by Western blot analysis.

    Silvestrol purchased from MCE. Usage Cited in: Antiviral Res. 2017 Dec 16;150:123-129.

    MRC-5 cells are infected with HCoV-229E at an MOI of 3 and treated with the indicated concentrations of silvestrol. Cell lysates are prepared at 12 h p.i. and 48 h p.i. as indicated and the accumulation of viral N and nsp8 proteins is determined by Western blot analysis.

    Silvestrol purchased from MCE. Usage Cited in: Viruses. 2018 Mar 27;10(4). pii: E149.

    A549 cells are infected with ZIKV U and treated with the indicated amount of Silvestrol. Cell lysates of the indicated time points are analyzed by Western blot with specific antibodies against NS1 and β-actin.

    Silvestrol purchased from MCE. Usage Cited in: Viruses. 2018 Mar 27;10(4). pii: E149.

    A549 cells are infected with ZIKV FP and treated with the indicated amount of Silvestrol. Cell lysates of the indicated time points are analyzed by Western blot with specific antibodies against NS1 and β-actin.

    Silvestrol purchased from MCE. Usage Cited in: Clin Cancer Res. 2018 Sep 1;24(17):4256-4270.

    Western blot showing protein expression of translationally regulated genes in DLBCL cells treated with DMSO (D), 50 nM Silvestrol (S) or 5 μM elatol for 16h. Representative images, n=3.

    Silvestrol purchased from MCE. Usage Cited in: Cancer Biology (Medicine), University of Miami. 2018 Jul.

    Western blot analysis of translationally regulates protein expression after 16h treatment.

    Silvestrol purchased from MCE. Usage Cited in: Viruses. 2018 Jun 2;10(6). pii: E301.

    Representative Western Blot of cellular lysates derived from cells treated with either 2 nM or 50 nM Silvestrol. DMSO treatment serves as control.

    Silvestrol purchased from MCE. Usage Cited in: Antiviral Res. 2018 Sep;157:151-158.

    Immunofluorescence staining of HEVp6 transfected Huh7.5 cells treated with Silvestrol (low concentration: 2.5 nM and medium concentration: 10 nM), Ribavirin or DMSO 4 h after transfection for 42 h.

    Silvestrol purchased from MCE. Usage Cited in: Viruses. 2018 Oct 30;10(11). pii: E592.

    Infection of 293T cells with CHIKV-mCherry in the presence of 50 nM silvestrol. Western blot analysis of cell lysates prepared from 293T cells infected with CHIKV-mCherry.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Silvestrol is a eukaryotic translation initiation factor 4A (eIF4A) inhibitor isolated from the fruits and twigs of Aglaia foveolata.

    IC50 & Target

    eIF4A[1]

    In Vitro

    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 IC50 values ranging from 1 to 7 nM[1]. 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[2]. 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 cisplatin[3]. 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[4].

    In Vivo

    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[5].

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 6.6 mg/mL (10.08 mM)

    H2O : < 0.1 mg/mL (insoluble)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.5275 mL 7.6376 mL 15.2751 mL
    5 mM 0.3055 mL 1.5275 mL 3.0550 mL
    10 mM 0.1528 mL 0.7638 mL 1.5275 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Silvestrol is prepared in 5.2% Tween 80 5.2% PEG 400[6].

    • 2.

      Silvestrol is dissolved in 20%(w/v) 2-hydroxyproply beta-cyclodextrin vehicle at a concentration of 125 μg/mL and injected into mice i.p.[7].

    • 3.

      Silvestrol is formulated in 30% 2-hydroxypropyl-β-cyclodextrin[8].

    References
    Kinase Assay
    [2]

    The Apo-ONETM homogeneous caspase-3/7 assay kit is used to measure the activities of caspase-3 and -7. Cells (7×104 cells/mL) are treated with Silvestrol (15 nM, 30 nM, 60 nM, 120 nM, and 240 nM) or etoposide for 24 h in a black 96-well plate. Etoposide, which is known to activate caspases-3/7 in LNCaP cells, is used as a positive control for this assay. At the end of the treatment, lysis buffer and the substrate (Z-DEVD-rhodamine 110) are mixed and added to the cells. Upon sequential cleavage and removal of the DEVD peptides by caspase-3 and -7 activity and excitation at 499 nm, the rhodamine 110-leaving group becomes intensely fluorescent. The emission maximum is 521 nm. The amount of fluorescent product generated is proportional to the amount of caspase-3 and -7 cleavage activity present in the sample. The samples are measured in triplicate. Caspase-3 and -7 activity is indicated by net fluorescence[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    The cells are seeded at a density of 7×104 cells/mL in 100-mm culture dishes and are treated with 30 nM or 120 nM concentrations of Silvestrol for 24 h. The cells are trypsinized, washed with PBS, and fixed with 1% (w/v) paraformaldehyde in PBS on ice for 30 min. After centrifugation, the cells are suspended in 70% (v/v) ethanol at −20°C until use. All ethanol is removed from the reaction tubes and cells are washed twice with PBS. The cells are processed for labeling with fluorescein-tagged deoxyuridine triphosphate nucleotide at 22°C-24°C overnight, washed, and incubated with propidium iodide/RNase A solution in the dark for 30 min at room temperature. The labeled cells are then analyzed by flow cytometry[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [5]

    Mice[5]
    Peripheral blood mononuclear cells (PBMC) are injected intraperitoneally (IP) into SCID mice depleted of murine natural killer (NK) cells by pretreatment (plus weekly re-treatment) with anti-asialo (GM1). Engraftment is confirmed by hu-IgG ELISA. Treatments with vehicle (30% hydroxypropyl-β-cyclodextrin) or Silvestrol (1.5 mg/kg every 48 hr IP) begin 2 weeks post-engraftment[5].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    654.66

    Formula

    C₃₄H₃₈O₁₃

    CAS No.

    697235-38-4

    SMILES

    O=C([[email protected]]([[email protected]]1C2=CC=CC=C2)[[email protected]@H](O)[[email protected]]3(O)[[email protected]@]1(C4=CC=C(OC)C=C4)OC5=CC(O[[email protected]@H]6O[[email protected]@H]([[email protected]](O)CO)CO[[email protected]]6OC)=CC(OC)=C35)OC

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 98.00%

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    Product Name:
    Silvestrol
    Cat. No.:
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    Cat. No.: HY-13251