Toosendanin
(Synonyms: 川楝素) 目录号 : GC38417
A triterpenoid with diverse biological activities
Cas No.:58812-37-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Toosendanin is a triterpenoid that has been found in M. toosendan and has diverse biological activities.1,2,3 It inhibits the proliferation of BEL-7404, U251, SH-SY5Y, HL-60, PC3, and U937 cancer cells (IC50s = <0.17 ?M for all).1 Toosendanin is larvicidal against A. aegypti first instar larvae (LC50 = 60.8 ?g/ml) and delays pupal development when used at concentrations ranging from 6.3 to 25 ?g/ml.2 It decreases serum levels of TNF-α, IL-1β, and IL-6 in a mouse model of ulcerative colitis induced by dextran sulfate (sodium salt) when administered at doses of 0.5 and 1 mg/kg.3 Toosendanin (9 mg/kg) increases survival in a mouse model of botulism induced by botulinum neurotoxin serotype A (BoNT/A).1
1.Shi, Y.-L., and Li, M.-F.Biological effects of toosendanin, a triterpenoid extracted from Chinese traditional medicineProg. Neurobiol.82(1)1-10(2007) 2.Ma, Z., Gulia-Nuss, M., Zhang, X., et al.Effects of the botanical insecticide, toosendanin, on blood digestion and egg production by female Aedes aegypti (Diptera: Culicidae): Topical application and ingestionJ. Med. Entomol.50(1)112-121(2013) 3.Fan, H., Chen, W., Zhu, J., et al.Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signalingInt. Immunopharmacol.76105909(2019)
| Cas No. | 58812-37-6 | SDF | |
| 别名 | 川楝素 | ||
| Canonical SMILES | C[C@@]1([C@H]2OC(C)=O)[C@@]3(O[C@@H]3C[C@H]1C4=COC=C4)[C@]5(C)[C@H](O)C[C@@]6([H])[C@]([C@@H](OC7)O)(C)[C@H](OC(C)=O)C[C@H](O)[C@]67[C@@]5([H])C2=O | ||
| 分子式 | C30H38O11 | 分子量 | 574.62 |
| 溶解度 | DMSO: 250 mg/mL (435.07 mM) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7403 mL | 8.7014 mL | 17.4028 mL |
| 5 mM | 0.3481 mL | 1.7403 mL | 3.4806 mL |
| 10 mM | 0.174 mL | 0.8701 mL | 1.7403 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
WWOX activation by Toosendanin suppresses hepatocellular carcinoma metastasis through JAK2/Stat3 and Wnt/β-catenin signaling
Cancer Lett 2021 Aug 10;513:50-62.PMID:34015398DOI:10.1016/j.canlet.2021.05.010.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Loss of WW-domain containing oxidoreductase (WWOX) has been proven to be associated with malignant metastasis in patients with HCC. In this study, by using a non-biased CRISPR knockout genetic screen targeting 19,050 human genes, we found that Toosendanin (TSN) is a novel druggable WWOX candidate agonist for metastatic HCC patients. We also found that TSN exhibited significant anti-proliferative and anti-metastatic effects on HCC cells in a WWOX-dependent manner. Overexpression and knockdown of WWOX in vitro and in vivo confirmed that the suppression of HCC by TSN involved WWOX. TSN regulated Stat3, DVL2, and GSK3β by transforming their interactions with WWOX as demonstrated by a Co-IP assay. TSN accelerated the degradation of β-catenin by promoting the function of APC, AXIN1, CK1, and GSK3β complex. Nuclear translocation of p-Stat3 Y705 and β-catenin was impeded by the TSN-induced blockade of JAK2/Stat3 and Wnt/β-catenin signaling, accompanied by the inhibition of MMPs and C-MYC.
Anti-cancer effect of Toosendanin and its underlying mechanisms
J Asian Nat Prod Res 2019 Mar;21(3):270-283.PMID:29629572DOI:10.1080/10286020.2018.1451516.
Toosendanin (TSN) is a triterpenoid purified from the medicinal herb Melia toosendan Sieb. et Zucc and has been used as an insecticide for decades. Recent studies have attracted increasing interest of TSN due to its novel anti-cancer effect in diverse cancer models. The broad spectrum anti-cancer activity suggests that TSN inhibits multiple pathways/targets that are critical for cancer cell survival and proliferation. Our recent study indicated that TSN has anti-cancer effect in glioblastoma through induction of estrogen receptor β (ERβ) and p53. This review highlights the anti-cancer efficacy of TSN and provides proof-of-principle insight into the underlying mechanisms.
Toosendanin, a novel potent vacuolar-type H+-translocating ATPase inhibitor, sensitizes cancer cells to chemotherapy by blocking protective autophagy
Int J Biol Sci 2022 Mar 28;18(7):2684-2702.PMID:35541921DOI:10.7150/ijbs.71041.
Macroautophagy/autophagy is the process of self-digestion through the lysosomes; it disassembles unnecessary or dysfunctional long-lived proteins and damaged organelles for the recycling of biomacromolecules. Unfortunately, cancer cells can hijack this mechanism to survive under metabolic stress or develop drug resistance during chemotherapy. Increasing evidence indicates that the combination of autophagy inhibition and chemotherapy is a promising cancer treatment strategy. However, effective autophagy inhibitors with satisfied potency, bioavailability, and clearly-defined drug targets are still rare. Here, we report the identification of a potent autophagy inhibitor Toosendanin which can effectively block autophagosome maturation, causing the accumulation of autophagy substrates in multiple cancer cells. Toosendanin did not inhibit the fusion process between autophagosome and lysosome but elevated lysosomal pH and impaired lysosomal enzymes activity. Using rat liver lysosome fraction and purified yeast V-ATPase, we found that Toosendanin directly inhibited V-ATPase activity. By applying cellular thermal shift assay (CETSA), immunoprecipitation-coupled LC-MS/MS analysis, and biotin-toosendanin pull-down assay, we confirmed the direct binding between Toosendanin and V-ATPase. Furthermore, Toosendanin blocked chemotherapy-induced protective autophagy in cultured cancer cells and xenograft tumor tissues to significantly enhance anti-cancer activity. These results suggest that Toosendanin has the potential to be developed into an anti-cancer drug by blocking chemotherapy-induced protective autophagy.
[Toosendanin induces apoptosis of human gastric cancer MGC-803 cells and its mechanism]
Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 May;37(3):262-265.PMID:34374238DOI:10.12047/j.cjap.6108.2021.004.
Objective: To explore the apoptosis of human gastric cancer MGC-803 cells induced by Toosendanin(TSN) and its mechanism. Methods: The human gastric cancer MGC-803 cells were divided into 5 groups, each group was set with 3 replicate. Fluorouracil (5-FU) and 0 nmol/L Toosendanin (TSN) were used as positive control and negative control, respectively. The other three groups were treated with Toosendanin at the final concentrations of 30, 50, and 70 nmol/L, respectively. After 48 h of treatment with Toosendanin, the morphology of the cells were observed under laser confocal microscopy. Flow cytometry was used to detect the mitochondrial membrane potential, and enzyme-labeled assays were used to detect the activities of Caspase-3 and Caspase-9. The mRNA and protein levels of Bcl-2, Bax, Cyt c and APAF-1 were measured by qRT-PCR and Western blot. Results: Compared with the 0 nmol/L TSN group, after the human gastric cancer MGC-803 cells were treated with Toosendanin at the concentrations of 30, 50, and 70 nmol/L for 48 h, the cell volume shrinkage, nucleus cleavage and chromatin morphological changes were observed under the microscope. The activities of Caspase-3 and Caspase-9 were increased significantly (P＜0.05), while the mitochondrial membrane potential was decreased significantly (P＜0.05). In addition, the mRNA and protein expression levels of Bax, Cyt c and APAF-1 were increased significantly (P＜0.05), while the mRNA and protein expression levels of Bcl-2 were decreased significantly (P＜0.05). Conclusion: Toosendanin up-regulates the expressions of Bax, Cyt c and APAF-1, down-regulates the expression of Bcl-2 gene, enhances the activities of caspase-3 and caspase-9, and induces the apoptosis of human gastric cancer MGC-803 cells.
Toosendanin Reprograms Macrophages to Enhance Antitumor Immunity
Cancer Discov 2023 Apr 3;13(4):OF7.PMID:36825930DOI:10.1158/2159-8290.CD-RW2023-030.
Toosendanin (TSN) converts macrophages from immunosuppressive to immunostimulatory in glioblastoma.