Rocaglamide (Roc-A), sourced from the Aglaia genus, is utilized for various ailments like coughs, injuries, asthma, and inflammatory skin disorders. It is a potent inhibitor of NF-κB activation in T-cells, a significant and selective suppressor of heat shock factor 1 (HSF1) activation with an IC50 value close to 50 nM, restricts the function of the translation initiation factor eIF4A, and exhibits anticancer effects, particularly against leukemia[1].[2].[3].
体内研究
In vivo studies show that tumor volumes in Rocaglamide-treated groups are reduced to 45±12% compared to the control group, indicating a significant suppression of tumor growth. Importantly, Rocaglamide treatment does not result in weight loss or display any signs of toxicity in mice, demonstrating its general tolerability[2].
体外研究
Rocaglamide effectively boosts TRAIL-induced apoptosis in resistant hepatocellular carcinoma (HCC) cells. Treatment with Rocaglamide alone induces apoptosis in 9% of HepG2 cells and 11% of Huh-7 cells, while TRAIL treatment leads to apoptosis in 16% of HepG2 and 17% of Huh-7 cells. Notably, the combined treatment with Rocaglamide and TRAIL induces apoptosis in 55% of HepG2 and 57% of Huh-7 cells, suggesting a synergistic effect. This enhanced apoptotic effect is also reflected in cell viability assessments via crystal violet staining. Thus, Rocaglamide has the potential to make highly chemoresistant HepG2 and Huh-7 cells more responsive to TRAIL-based treatments[2].
Rocaglamide/楝酰胺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Healthy peripheral blood T cells
100 nM
16 hours
Roc-AR does not sensitize healthy T cells to CD95L and TRAIL-induced apoptosis
Cell Death Differ. 2011 Feb;18(2):362-70.
HeLa cells
50 nM
24 hours
FL3 treatment potently inhibited PINK1-PRKN-mediated mitophagy, blocking the recruitment and accumulation of PRKN and PINK1 on mitochondria
Autophagy. 2020 Mar;16(3):419-434.
HCT116 cells
50 nM
24 hours
FL3 or Roc-A treatment markedly increased the protein level of PARL but had no effect on the protein levels of PHB and PHB2
Autophagy. 2020 Mar;16(3):419-434.
H460 cells
0, 31.25, 62.5, 125, 250 and 500 nM
24 hours
To evaluate the effect of RocA on NK cell-mediated lysis of H460 cells, results showed that RocA enhanced NK cell-mediated lysis of H460 cells.
Autophagy. 2018;14(10):1831-1844.
H1975 cells
250 nM
24 hours
To evaluate the effect of RocA on NK cell-mediated lysis of H1975 cells, results showed that RocA enhanced NK cell-mediated lysis of H1975 cells.
Autophagy. 2018;14(10):1831-1844.
A549 cells
250 nM
24 hours
To evaluate the effect of RocA on NK cell-mediated lysis of A549 cells, results showed that RocA enhanced NK cell-mediated lysis of A549 cells.
Autophagy. 2018;14(10):1831-1844.
A549 cells
12.5 nM and 25 nM
24 hours
RocA significantly increased the expression of CCL5 in A549 cells
Int J Biol Sci. 2022 Jan 1;18(2):585-598.
H1299 cells
12.5 nM and 25 nM
24 hours
RocA significantly increased the expression of CCL5 in H1299 cells
Int J Biol Sci. 2022 Jan 1;18(2):585-598.
H1975 cells
12.5 nM and 25 nM
24 hours
RocA significantly increased the expression of CCL5 in H1975 cells
Int J Biol Sci. 2022 Jan 1;18(2):585-598.
LLC cells
25 nM and 50 nM
24 hours
RocA significantly increased the expression of CXCL10 in LLC cells
Int J Biol Sci. 2022 Jan 1;18(2):585-598.
U87MG
6.25 nM
24 hours
To investigate the effects of Rocaglamide on the translation machinery and protein output in U87MG cells, it was found that it induced the expression of specific proteins and activated the JNK signaling pathway.
Cell Rep. 2021 Oct 12;37(2):109806.
Human peripheral blood T lymphocytes
75 nM
24 hours
Roc-A significantly reduced apoptosis in T cells induced by DNA-damaging anticancer drugs, with a dose-dependent protective effect.
Cell Death Dis. 2014 Jan 16;5(1):e1000.
Human peripheral blood B cells
75 nM
24 hours
Roc-A significantly reduced apoptosis in B cells induced by Etoposide.
Cell Death Dis. 2014 Jan 16;5(1):e1000.
Human peripheral blood NK cells
75 nM
24 hours
Roc-A significantly reduced apoptosis in NK cells induced by Etoposide.
Cell Death Dis. 2014 Jan 16;5(1):e1000.
Human neutrophils
75 nM
24 hours
Roc-A significantly reduced apoptosis in neutrophils induced by Etoposide.
Cell Death Dis. 2014 Jan 16;5(1):e1000.
Human cardiomyocytes
75 nM
24 hours
Roc-A significantly reduced apoptosis in cardiomyocytes induced by Etoposide.
Cell Death Dis. 2014 Jan 16;5(1):e1000.
Murine hematopoietic stem and progenitor cells
75 nM
24 hours
Roc-A significantly reduced apoptosis in murine hematopoietic stem and progenitor cells induced by Etoposide.
Cell Death Dis. 2014 Jan 16;5(1):e1000.
HEK 293 cells
30 nM
30 minutes
RocA treatment caused a dose-dependent decrease in polysome formation and protein synthesis, inhibiting translation without causing 4EBP dephosphorylation or eIF2α phosphorylation, but partially rescued by expression of RocA-resistant eIF4A proteins.
Nature. 2016 Jun 23;534(7608):558-61.
HEK293 cells
0.3 µM, 3 µM
30 minutes
To investigate the perturbation of translation elongation dynamics by RocA, it was found that RocA selectively perturbed the early translation elongation of a set of genes, leading to ribosome collision and reduction of protein synthesis.
Nat Commun. 2023 Feb 2;14(1):553.
HEK293 cells
0.3 µM
30 minutes
To evaluate the effect of RocA on translation in HEK293 cells using ribosome profiling, results showed that RocA significantly inhibited the translation of specific mRNAs.
Roc-AR inhibits c-FLIP expression and enhances TRAIL and CD95L-induced apoptosis
Cell Death Differ. 2011 Feb;18(2):362-70.
SP cells
100 nM
4 hours
Roc-AR inhibits c-FLIP expression and enhances TRAIL- and CD95L-induced apoptosis
Cell Death Differ. 2011 Feb;18(2):362-70.
CHAMP cells
100 nM
4 hours
Roc-AR inhibits c-FLIP expression and enhances TRAIL- and CD95L-induced apoptosis
Cell Death Differ. 2011 Feb;18(2):362-70.
M9-ENL cell line
40 nM
48 hours
Rocaglamide was significantly more cytotoxic to leukemia cells compared to other translation inhibitors such as Temsirolimus.
Leukemia. 2014 Oct;28(10):1960-8.
HEK293 cells
0-10 nM
72 hours
To assess the effect of RocA on the viability of HEK293 cells, results showed that RocA significantly inhibited cell viability at low concentrations.
Mol Cell. 2019 Feb 21;73(4):738-748.e9.
Rocaglamide/楝酰胺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Foxp3DTR mice
Intraperitoneal injection
0.2 mg/kg
Once daily for 8 days
To test whether RocA could alleviate inflammation caused by Treg depletion, results showed that RocA significantly reduced weight loss and decreased the number of splenic CD4 T cells producing IL-17A or IFNγ.
J Exp Med. 2023 Mar 6;220(3):e20221676
SCID/Bg mice
H1975 cell subcutaneous xenograft tumor model
Intraperitoneal injection
0.3 mg/kg
Every 2 days, until day 21
To evaluate the inhibitory effect of RocA on H1975 cell subcutaneous xenograft tumors, results showed that RocA significantly inhibited tumor growth.
Autophagy. 2018;14(10):1831-1844.
Mice
Patient-derived xenograft model
Intraperitoneal injection
1 mg/kg
Once daily for 3 days
To investigate the effects of Rocaglamide on tumors in vivo, it was found that it induced GEF-H1 protein expression and JNK phosphorylation, leading to tumor cell death.
Cell Rep. 2021 Oct 12;37(2):109806.
C57BL/6 mice
LLC cell subcutaneous xenograft model
Intraperitoneal injection
1.0 mg/kg
Every 2 days for 18 days
RocA significantly increased the infiltration of NK cells in tumors and inhibited tumor growth
搜索
