| Description | Rocaglamide (Roc-A), isolated from the genus Aglaia, can be used to treat coughs, injuries, asthma, and inflammatory skin diseases. It is a potent inhibitor of NF-κB activation in T-cells. |
| In vitro | Rocaglamide是一种有效且选择性的热休克因子1（HSF1）激活抑制剂，IC50约为50 nM。它通过抑制转录启动因子eIF4A的功能发挥作用，并且具有针对白血病[1,2,3]的抗癌特性。单独使用Rocaglamide可导致9%的HepG2细胞和11%的Huh-7细胞发生凋亡，而与TRAIL联合治疗则分别使16%的HepG2细胞和17%的Huh-7细胞发生凋亡。然而，Rocaglamide与TRAIL的组合使用在HepG2和Huh-7细胞中引发的凋亡率分别高达55%和57%，明显超出了简单加成效应[2]。 |
| In vivo | 在Rocaglamide处理组中，肿瘤体积与对照组相比为45±12%。Rocaglamide显著抑制肿瘤生长，与对照组相比有明显差异。使用Rocaglamide治疗期间，小鼠体重没有减少，且未观察到明显的毒性迹象[2]。 |
| Cell experiments | HepG2 and Huh-7 cells (1×10^4/well) are seeded in 96-well plates in complete culture medium and incubated for 24 h. The cells are then exposed to 100 nM Rocaglamide and/or 100 ng/mL TRAIL for 24 h. The control cells are treated with DMSO at a concentration equal to that used for the drug-treated cells. The complete culture medium is then removed and MTT (200 μL, 0.5 mg/mL in 10% FBS-containing DMEM) is added to each well and the plate is incubated for 2 h at 37°C in a humidified incubator. The solution is then removed from the wells and 200 μL DMSO is added to each well prior to agitation. The absorbance at 570 nm is read using a microplate reader (Bio-Tek ELx800). The value for the vehicle-treated cells is considered to indicate 100% viability. Furthermore, a crystal violet assay is carried out. Briefly, the cells (1×10^5/mL) are seeded in a 12 well plate for 12 h and treated with TRAIL (0-100 ng/mL) and/or RocA(1-100 nM) for 12 h. The treated cells are washed with phosphate-buffered saline (PBS), fixed with 4% paraformaldehyde for 15 min, and stained using crystal violet for a further 30 min [2]. |
| Animal experiments | The Huh-7 cells (3×10^6), suspended in 100 μL mix (equal volumes of DMEM and Matrigel), are implanted subcutaneously into the right flank of 10 female SCID mice (6-week-old) and then randomly divided into two equal groups, one of which received an intraperitoneal injection of Rocaglamide (2.5 mg/kg in 80 μL olive oil; n=5) and the other, used as a vehicle control, received olive oil alone (n=5). These treatments are performed once daily for 32 days and the tumor volumes and body weights of the animals are measured twice a week. The tumor volumes (mm3) are calculated using the following formula: Tumor volume=LS2/2, where L is the longest diameter and S is the shortest. At the end of the experiments, the mice are sacrificed and tumor samples are harvested, fixed in formalin and embedded in paraffin as tissue sections for immunohistochemical analysis [2]. |
| Target activity | HSF1:50 nM |
| Synonyms | Rocaglamide A, 楝酰胺, Roc-A |
| molecular weight | 505.56 |
| Molecular formula | C29H31NO7 |
| CAS | 84573-16-0 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 10 mg/mL (19.78 mM) Ethanol: 5 mg/mL (9.89 mM) |
| References | 1. Santagata S, et al. Tight coordination of protein translation and heat shock factor 1 activation supports the anabolic malignant state. Science. 2013 Jul 19; 341(6143): 1238303. 2. Luan Z, 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. 3. Baumann B, 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. |