Rocaglamide (Rocaglamide A)

Rocaglamide (Rocaglamide A) is isolated from the genus Aglaia (family Meliaceae). Rocaglamide (Rocaglamide A)(IC50 of 50 nM) inhibits the function of the translation initiation factor eIF4A, a DEAD box RNA helicase ^[1，2].

Rocaglamide (Rocaglamide A) (100 nM;24h) significantly enhanced TRAIL induced apoptosis^[4]. Rocaglamide (Rocaglamide A) (20- 100 nM;48h)can induce 10-30% apoptosis of L1236 and KM-H2 cells ^[3]. Rocaglamide (Rocaglamide A) are able to suppress the PMA-induced expression of NF-kappaB target genes and sensitize leukemic T cells to apoptosis induced by TNFalpha, cisplatin, and gamma-irradiation ^[5]. Rocaglamide (Rocaglamide A)( 30/50 nM;21d) prevented TNF-α mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells ^[6].

Rocaglamide (Rocaglamide A)( 2.5 mg/kg; i.p.; 32 days) induced tumor cell apoptosis in a SCID mouse model (Huah-7 cells) without causing weight loss in mice, and no significant signs of toxicity were observed during treatment, suggesting that Rocaglamide is generally well tolerated in vivo^[4]. Rocaglamide (Rocaglamide A)( 0.5 mg/kg; i.p.; five times per week for two weeks) overcomes CPT resistance in U266 in vitro and significant increases in anti-tumor efficacies of CPT in mice xenografted with U266^[7].

References:
[1]. Santagata S, Mendillo ML, et,al. Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science. 2013 Jul 19;341(6143):1238303. doi: 10.1126/science.1238303. PMID: 23869022; PMCID: PMC3959726.
[2]. Kim S, Salim AA, Swanson SM and Kinghorn AD: Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy. Anticancer Agents Med Chem. 6:319-345. 2006.
[3]. Giaisi M, K?hler R, et,al. Rocaglamide and a XIAP inhibitor cooperatively sensitize TRAIL-mediated apoptosis in Hodgkin's lymphomas. Int J Cancer. 2012 Aug 15;131(4):1003-8. doi: 10.1002/ijc.26458. Epub 2011 Nov 8. PMID: 21952919.
[4]. Luan Z, He Y, et,al. Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation. Mol Med Rep. 2015 Jan;11(1):203-11. doi: 10.3892/mmr.2014.2718. Epub 2014 Oct 21. PMID: 25333816; PMCID: PMC4237083.
[5]. Baumann B, Bohnenstengel F, et,al. Rocaglamide derivatives are potent inhibitors of NF-kappa B activation in T-cells. J Biol Chem. 2002 Nov 22;277(47):44791-800. doi: 10.1074/jbc.M208003200. Epub 2002 Sep 16. PMID: 12237314.
[6]. Li A, Yang L, et,al. Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling. Mol Cells. 2015 Nov;38(11):941-9. doi: 10.14348/molcells.2015.2353. Epub 2015 Nov 6. PMID: 26549505; PMCID: PMC4673408.
[7]. Wu Y, Giaisi M, et,al. Rocaglamide breaks TRAIL-resistance in human multiple myeloma and acute T-cell leukemia in vivo in a mouse xenogtraft model. Cancer Lett. 2017 Mar 28;389:70-77. doi: 10.1016/j.canlet.2016.12.010. Epub 2016 Dec 18. PMID: 27998762.

Rocaglamide (Rocaglamide A) 是从 Aglaia 属（楝科）中分离出来的。 Rocaglamide (Rocaglamide A)(IC50为50 nM)抑制翻译起始因子eIF4A的功能，eIF4A是一种DEAD box RNA解旋酶^[1，2]。

Rocaglamide (Rocaglamide A) (100 nM;24h) 显着增强 TRAIL 诱导的细胞凋亡^[4]。 Rocaglamide (Rocaglamide A) (20- 100 nM;48h) 可诱导 L1236 和 KM-H2 细胞 10-30% 的凋亡^[3]。 Rocaglamide (Rocaglamide A) 能够抑制 PMA 诱导的 NF-kappaB 靶基因表达，并使白血病 T 细胞对 TNFalpha、顺铂和伽马射线照射诱导的细胞凋亡敏感^[5]。 Rocaglamide (Rocaglamide A)( 30/50 nM;21d) 在 C2C12 和原代间充质基质细胞中阻止 TNF-α 介导的成骨细胞分化抑制，并直接促进成骨细胞分化^[6]。

Rocaglamide (Rocaglamide A)（2.5 mg/kg；i.p.；32 天）在 SCID 小鼠模型（Huah-7 细胞）中诱导肿瘤细胞凋亡，而不会导致小鼠体重减轻，并且在治疗期间未观察到明显的毒性迹象治疗，表明 Rocaglamide 在体内通常具有良好的耐受性^[4]。 Rocaglamide (Rocaglamide A)（0.5 mg/kg；腹腔注射；每周 5 次，持续两周）在体外克服了 U266 的 CPT 耐药性，并显着提高了 U266 异种移植小鼠的 CPT 抗肿瘤功效^{[7]< /sup>.}