1. Apoptosis
  2. Caspase

Silvestrol (Synonyms: (-)-Silvestrol)

Cat. No.: HY-13251 Purity: 99.28%
Data Sheet SDS Handling Instructions

Silvestrol is isolated from the fruits and twigs of Aglaia foveolata, by inducing caspase-3 activation to cause cell death.

For research use only. We do not sell to patients.
Silvestrol Chemical Structure

Silvestrol Chemical Structure

CAS No. : 697235-38-4

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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. 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: bioRxiv. Sep. 27, 2017.

    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.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Silvestrol is isolated from the fruits and twigs of Aglaia foveolata, by inducing caspase-3 activation to cause cell death.

    In Vitro

    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. So that these pathways do not play a crucial role in silvestrol-induced apoptosis[1]. 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[2]. 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[3].

    In Vivo

    silvestrol (1.5 mg/kg) 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[4].

    References
    Preparing Stock Solutions
    Concentration Volume 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.
    Kinase Assay
    [1]

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

    Cell Assay
    [1]

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

    Animal Administration
    [4]

    Silvestrol is formulated in 30% hydroxypropyl-β-cyclodextrin.

    PBMC are injected intraperitoneally (IP) into SCID mice depleted of murine 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. 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

    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

    Solvent & Solubility

    DMSO; H2O: < 1 mg/mL

    Silvestrol is prepared in 5.2% Tween 80 5.2% PEG 400[5].
    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.[6].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

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    Product Name:
    Silvestrol
    Cat. No.:
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