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Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma.
For research use only. We do not sell to patients.
Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma[1][2][3][4][5][6][7][8][9][10][11].
In Vitro
Raddeanin A (0.2-0.8 μM; 3-7 days) potently inhibits RANKL-induced osteoclast formation in BMMs, with a 72-hour cytotoxicity IC50 of 2.91 μM, and suppresses osteoclast survival in a concentration-dependent manner[1]. Raddeanin A (0.4 μM; 5-7 days) downregulates key osteoclastogenic markers CTSK and NFATc1 at both the gene and protein levels in RANKL-stimulated BMMs[1]. Raddeanin A (0.2-0.8 μM; 7-21 days), at concentrations up to 0.8 μM, does not inhibit osteoblast differentiation in MC3T3-E1 cells, and at 0.2 μM enhances mineralization and increases SPARC gene expression[1]. Raddeanin A (6.25-50 μM; 24-96 h) inhibits viability, proliferation, and invasion of MDA-MB-231 breast cancer cells, and induces apoptosis, with a 96-hour cytotoxicity IC50 of 15.77 μM[1]. Raddeanin A (3 μM; 6-12 h) inhibits AKT/mTOR signaling in MDA-MB-231 cells by reducing p-AKT and mTOR protein levels[1]. Raddeanin A (0.2-50 μM; 24-48 h) dose- and time-dependently inhibits the viability of human osteosarcoma MG-63, HOS, U-2 OS, Saos-2, and 143B cells, with MG-63 and HOS cells showing the highest sensitivity (IC50 values of 1.60 μM and 2.57 μM at 48 h, respectively)[2]. Raddeanin A (1-4 μM; 24 h) dose-dependently modulates mitochondrial apoptotic pathway proteins (reducing Bcl-2/Bax ratio, increasing cleaved caspase-3 and cleaved PARP) in human osteosarcoma MG-63 and HOS cells[2]. Raddeanin A (1-4 μM; 12 h) dose-dependently inhibits IκBα phosphorylation in human osteosarcoma MG-63 and HOS cells after 12 h of treatment[2]. Raddeanin A (1-4 μM; 2 μM, 6 h) dose-dependently suppresses p65 nuclear translocation in human osteosarcoma MG-63 and HOS cells, with 2 μM treatment for 6 h visibly reducing nuclear p65 localization[2]. Raddeanin A (100-800 nM; 48 h) dose-dependently reduces the viability of U87, U251, T98G, and LN299 human glioblastoma cells, with greater potency in U87 and U251 cells[4]. Raddeanin A (100-200 nM; 48 h) dose-dependently reduces the mRNA and protein expression of β-catenin and EMT-related biomarkers (N-cadherin, vimentin, snail) in U87 and U251 human glioblastoma cells[4]. Raddeanin A (100 nM) inhibits viability, migration, invasion, and EMT biomarker expression in β-catenin-overexpressing U87 and U251 human glioblastoma cells, but these effects are reversed by β-catenin overexpression[4]. Raddeanin A (0.125-0.5 μM; 24 h) inhibits Aβ1-42-induced activation of the NLRP3 inflammasome and secretion of inflammatory cytokines in MIO-M1 cells[5]. Raddeanin A (0-160 μg/mL; 24 h) reduces cell viability in a dose-dependent manner in RBE, LIPF155C, LIPF178C, and LICCF cholangiocarcinoma cell lines (EC50: 50.95-64.76 μg/mL; LC50: 34.65-49.47 μg/mL) with lower toxicity to normal HIBEpiC biliary epithelial cells[6]. Raddeanin A (1-5 μM; 20 h) dose-dependently increases HMGB1-Gluc activity, a marker of immunogenic cell death, in B16 and MC38 cells[7]. Raddeanin A (1-5 μM; 6-8 h) dose-dependently increases mitochondrial ROS production in MC38 cells[7]. Raddeanin A (1-4 μM; 24 h) dose-dependently inhibits the migration and invasion of H1299, A549, and PC-9 NSCLC cells after 24 h of treatment[8]. Raddeanin A (1-4 μM; 24 h) modulates EMT-related protein expression and specifically inhibits CDK6 expression and Rb phosphorylation in H1299, A549, and PC-9 NSCLC cells after 24 h of treatment[8]. Raddeanin A (1-4 μM; 24 h) dose-dependently induces G1 phase cell cycle arrest in H1299, A549, and PC-9 NSCLC cells after 24 h of treatment[8]. Raddeanin A (1-16 μM; 12 h) potently inhibits proliferation of human colorectal cancer HCT116 cells in a dose-dependent manner, with a 12 h IC50 of 2.61 μM[9]. Raddeanin A (2-4 μM; 12 h) dose-dependently downregulates the mRNA expression of apoptosis-related genes (caspase-3, PARP) and cell cycle-related genes (cyclinD1, cyclinE) in human colorectal cancer HCT116 cells[9]. Raddeanin A (2-4 μM; 12 h) modulates protein expression in human colorectal cancer HCT116 cells by increasing pro-apoptotic proteins, decreasing anti-apoptotic and cell cycle-related proteins, and suppressing the PI3K/AKT signaling pathway via reduced p-PI3K and p-AKT expression[9]. Raddeanin A (1.5-6 μM; 12-72 h) dose- and/or time-dependently inhibits the growth of AR-positive 22Rv1, C4-2, C4-2B, and LNCaP95 CRPC cells, with no effect on AR-null PC-3 and DU145 prostate cancer cells[10]. Raddeanin A (3 μM; 6-24 h) time-dependently downregulates mRNA levels of AR target genes PSA (in C4-2 and LNCaP95 cells) and UBE2C (in LNCaP95 cells)[10]. Raddeanin A (0.125-8 μM; 24-48 h) inhibits the proliferation of MM.1S, MM.1R, and RPMI 8226 multiple myeloma cells in a time-dependent and concentration-dependent manner, with IC50 values ranging from 1.058 μM (MM.1S, 48 h) to 6.091 μM (RPMI 8226, 24 h)[11].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
RANKL-induced mouse bone marrow-derived macrophages (BMMs)
Concentration:
0.4 μM
Incubation Time:
5 days; 7 days
Result:
Dramatically suppressed mRNA expression of cathepsin k (CTSK) and nuclear factor of activated T cells 1 (NFATc1). Reduced protein expression levels of CTSK and NFATc1.
Showed no significant difference in ALP activity between control and treated groups at day 7. Resulted in a larger total mineralized area compared to the control group at 0.2 μM at day 21. Significantly increased secreted protein acidic and rich in cysteine (SPARC) mRNA expression after 14 days of treatment. Showed no significant cytotoxic effect on MC3T3-E1 cells at doses below 0.781 μM.
Caused a dose-dependent increase in the percentage of both early and late apoptotic cells in MG-63 and HOS cells.
In Vivo
Raddeanin A (50-100 μg/kg; daily; 14 days) significantly inhibits Ti-particle-induced calvarial osteolysis in male C57BL/6 mice by reducing osteoclast formation and bone resorption, as evidenced by increased BV/TV, decreased porosity, and fewer TRAP- and CTSK-positive osteoclasts[1]. Raddeanin A (100 μg/kg; i.p.; every other day; 28 days) significantly inhibits breast cancer-induced osteolysis in female BALB/c nu/nu mice by preserving bone structure and increasing tumor cell apoptosis, as evidenced by higher BV/TV, reduced Tb. Sp, intact bone cortex, and increased TUNEL-positive cells[1]. Raddeanin A (1.25-5 mg/kg; i.p.; every other day; 20 consecutive days) dose-dependently inhibits the growth of HOS osteosarcoma xenografts in nude mice, while inducing tumor cell apoptosis and demonstrating low systemic toxicity[2]. Raddeanin A (0.4 μM; continuous immersion; 30 h) inhibits zebrafish intersegmental vessel formation by 67.64%[3]. Raddeanin A (5 mg/kg; i.p.; once every 2 days; 11 injections) reduces HCT-15 colorectal xenograft tumor volume and weight, increases tumor apoptosis and necrosis, and decreases intratumoral microvessel density without obvious toxicity[3]. Raddeanin A (100 mg/kg; i.p.; daily) inhibits glioblastoma tumor growth, reduces tumor vessel density, downregulates β-catenin-mediated EMT and angiogenesis, and increases survival rate to ~80% at day 30 in an intracranial U87 xenograft mouse model[4]. Raddeanin A (10 mg/kg; p.o.; daily; 9 weeks) protects the blood-retinal barrier and improves Alzheimer's disease-related retinopathy in 3×Tg-AD mice by inhibiting NLRP3-mediated inflammation, suppressing Wnt/β-catenin pathway-mediated apoptosis, and restoring retinal structural and vascular integrity[5]. Raddeanin A (1-4 mg/kg; i.p., i.t.; four times at indicated time points) inhibits MC38 colon adenocarcinoma growth in a DC and CD8+ T cell-dependent manner in C57BL/6J mice, and induces 60% tumor-free survival in a tumor rechallenge model[7]. Raddeanin A (4 mg/kg; i.t.; four times at indicated time points)'s antitumor activity against MC38 colon adenocarcinoma in C57BL/6J mice is dependent on CD8+ T cells and DCs, and combining it with anti-PD-1 antibody enhances therapeutic efficacy by reprogramming the tumor immune microenvironment[7]. Raddeanin A (0.5-1.0 mg/kg; i.p.; once every 2 days; 7 total doses over 30 days) exerts dose-dependent anti-NSCLC efficacy in BALB/c nude mouse xenografts, with the 1.0 mg/kg dose significantly reducing tumor volume and weight while showing no detectable organ toxicity[8]. Raddeanin A (4 mg/kg; injected; 2 weeks) significantly inhibits colorectal cancer xenograft tumor growth in BALB/c nude mice, reduces tumor volume and weight, induces tumor cell apoptosis at a rate of 43.6%, modulates apoptosis- and cell cycle-related proteins, and regulates the PI3K/AKT signaling pathway without causing liver toxicity[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Increased bone volume to total volume (BV/TV) ratio compared to vehicle group. Decreased percentage of total porosity compared to vehicle group. Reduced number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts compared to vehicle group. Reduced number of cathepsin K (CTSK)-positive multinucleated osteoclasts compared to vehicle group.
Animal Model:
BALB/c nu/nu (5-week-old female; breast cancer-induced osteolysis model)[1]
Dosage:
100 μg/kg
Administration:
i.p.; every other day; 28 days
Result:
Increased trabecular bone volume to total volume (BV/TV) ratio compared to vehicle group. Reduced trabecular separation (Tb. Sp) compared to vehicle group. Preserved intact bone cortex (versus extensive trabecular bone resorption and discrete cortical bone in vehicle controls). Increased apoptosis in the treated group, as shown by TUNEL assay.
Significantly decelerated tumor growth in a dose-dependent manner. Reduced tumor volumes in all treatment groups. Induced significant apoptosis in tumor tissues via TUNEL staining. Increased p-JNK protein expression and decreased p65 protein expression in tumor tissues via immunohistochemistry analysis. Caused no significant body weight loss during treatment.
Reduced mean tumor volume to 765.3 mm3. Reduced mean tumor weight to 1.2 g. Decreased intratumoral microvessel density to ~20 vessels/mm2. Increased the percentage of TUNEL-positive apoptotic cells to ~60%. Increased tumor necrosis area to ~70%. Caused no significant body weight loss.
Significantly reduced the number of degenerated retinal capillaries compared to untreated 3×Tg-AD mice. Increased retinal expression of tight junction proteins ZO-1, Occludin, and Claudin 5. Ameliorated retinal structural abnormalities: restored total retinal thickness, ganglion cell layer + inner plexiform layer thickness, inner nuclear layer thickness, and outer nuclear layer thickness; improved disorganization of retinal cell layers. Increased the Bcl-2/Bax protein expression ratio in retinal tissue. Reduced retinal expression of NLRP3 inflammasome components (NLRP3, pro-Caspase-1, Caspase-1, ASC) and pro-inflammatory cytokines (IL-1β, IL-18). Decreased retinal expression of β-catenin and phosphorylated LRP5/6, and increased retinal expression of GSK-3β, indicating inhibition of the Wnt/β-catenin pathway.
i.p., four times at indicated time points; i.t., four times at indicated time points
Result:
Caused considerable inhibition of tumor volume and tumor weight. Induced 60% tumor-free survival 30 days after rechallenge with live MC38 cells. Markedly elevated the population of tumor-infiltrating CD8+ T cells and CD103+CD11c+ DCs, and increased levels of CD8+ T cell effector molecules GZMB and IFN-γ within the tumor microenvironment. Upregulated CD40, CD80, CD86, and MHC-II expression on tumor-infiltrating CD103+CD11c+ DCs.
Had its MC38 tumor inhibition attenuated by anti-CD8 depletion antibody. Had its MC38 tumor growth inhibition abolished by DC depletion via cytochrome c. When combined with anti-PD-1 antibody, achieved greater tumor growth inhibition than either treatment alone, increased populations of tumor-infiltrating CD8+ T cells and CD103+CD11c+ DCs, increased cleaved caspase 3 levels, decreased populations of regulatory T cells and monocytic MDSCs, and upregulated CD40, CD80, CD86, and MHC-II expression on tumor-infiltrating CD103+CD11c+ DCs.
DMSO : 50 mg/mL (55.74 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
1.1147 mL
5.5735 mL
11.1470 mL
5 mM
0.2229 mL
1.1147 mL
2.2294 mL
10 mM
0.1115 mL
0.5574 mL
1.1147 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.79 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (2.79 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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