Silvestrol is a eukaryotic translation initiation factor 4A (eIF4A) inhibitor isolated from the fruits and twigs of Aglaia foveolata. Silvestrol induces autophagy and caspase-mediated apoptosis[1][2][3].
IC50 & Target
eIF4A[1]
体外研究 (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 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]. 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[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
654.66
Formula
C34H38O13
CAS 号
697235-38-4
运输条件
Room temperature in continental US; may vary elsewhere.
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].
参考文献
[1]. Chambers JM, et al. Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Org Lett. 2013 Mar 15;15(6):1406-9.
[2]. Kim S, et al. Silvestrol, a potential anticancer rocaglate derivative from Aglaia foveolata, induces apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7. Anticancer Res. 2007 Jul-Aug;27(4B):2175-83.
[3]. Chen WL, et al. Silvestrol induces early autophagy and apoptosis in human melanoma cells. BMC Cancer. 2016 Jan 13;16:17.
[4]. Daker M, et al. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of CDDP with silvestrol and episilvestrol isolated from Aglaia stellatopilosa. Exp Ther Med. 2016 Jun;11(6):2117-2126.
[5]. Patton JT, et al. The translation inhibitor silvestrol exhibits direct anti-tumor activity while preserving innate and adaptive immunity against EBV-driven lymphoproliferative disease. Oncotarget. 2015 Feb 20;6(5):2693-708.
[6]. Wolfe AL, et al. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature. 2014 Sep 4;513(7516):65-70.
[7]. Wiegering A, et al. Targeting Translation Initiation Bypasses Signaling Crosstalk Mechanisms That Maintain High MYC Levels in Colorectal Cancer. Cancer Discov. 2015 Jul;5(7):768-781.
[8]. Todt D, et al. The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo. Antiviral Res. 2018 Sep;157:151-158.
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[2].
上海金畔生物科技有限公司 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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Chambers JM, et al. Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Org Lett. 2013 Mar 15;15(6):1406-9.
[2]. Kim S, et al. Silvestrol, a potential anticancer rocaglate derivative from Aglaia foveolata, induces apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7. Anticancer Res. 2007 Jul-Aug;27(4B):2175-83.
[3]. Chen WL, et al. Silvestrol induces early autophagy and apoptosis in human melanoma cells. BMC Cancer. 2016 Jan 13;16:17.
[4]. Daker M, et al. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of CDDP with silvestrol and episilvestrol isolated from Aglaia stellatopilosa. Exp Ther Med. 2016 Jun;11(6):2117-2126.
[5]. Patton JT, et al. The translation inhibitor silvestrol exhibits direct anti-tumor activity while preserving innate and adaptive immunity against EBV-driven lymphoproliferative disease. Oncotarget. 2015 Feb 20;6(5):2693-708.
[6]. Wolfe AL, et al. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature. 2014 Sep 4;513(7516):65-70.
[7]. Wiegering A, et al. Targeting Translation Initiation Bypasses Signaling Crosstalk Mechanisms That Maintain High MYC Levels in Colorectal Cancer. Cancer Discov. 2015 Jul;5(7):768-781.
[8]. Todt D, et al. The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo. Antiviral Res. 2018 Sep;157:151-158.
