Bigelovin
(Synonyms: 锦菊素) 目录号 : GC60076
Bigelovin是可从海百合中分离得到的一种倍半萜内酯，是选择性的视黄素X受体α(retinoidXreceptorα)的激动剂。Bigelovin可通过诱导凋亡和自噬来发挥抗肿瘤活性。Bigelovin通过抑制ROS的生成来调节mTOR信号通路。
Cas No.:3668-14-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bigelovin, a sesquiterpene lactone isolated from Inula helianthus-aquatica, is a selective retinoid X receptor α agonist. Bigelovin suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation[1].
Bigelovin (0-20 μM, 24-72 h) significantly inhibits cell viability of liver cancer cells and induces apoptosis and autophagy[1].Bigelovin causes a significant increase of p62, LC3B-II, Beclin-1 and a corresponding decrease of p62 levels in a time-dependent manner[1].Bigelovin induces cell death involves the suppression of mTOR pathway regulated by ROS production[1]. Cell Viability Assay[1] Cell Line: HepG2 and SMMC-7721 cells.
Bigelovin (BigV, 5, 10, 20 mg/kg) exerts anti-tumor activity in HepG2 xenograft tumor model[1]. Animal Model: HepG2 xenograft model based on the male athymic BALB/c nude mice (5-6 weeks old, 18-22 g)[1].
[1]. Bei Wang, et al. Bigelovin, a sesquiterpene lactone, suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation in liver cancer. Biochem Biophys Res Commun. 2018 May 5;499(2):156-163.
| Cas No. | 3668-14-2 | SDF | |
| 别名 | 锦菊素 | ||
| Canonical SMILES | C[C@@]12C(C=C[C@]1([C@@H](C[C@]3([C@H]([C@@H]2OC(C)=O)C(C(O3)=O)=C)[H])C)[H])=O | ||
| 分子式 | C17H20O5 | 分子量 | 304.34 |
| 溶解度 | 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 | 3.2858 mL | 16.429 mL | 32.858 mL |
| 5 mM | 0.6572 mL | 3.2858 mL | 6.5716 mL |
| 10 mM | 0.3286 mL | 1.6429 mL | 3.2858 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。
Sesquiterpene lactone Bigelovin induces apoptosis of colon cancer cells through inducing IKK-β degradation and suppressing nuclear factor kappa B activation
Anticancer Drugs 2021 Jun 1;32(6):664-673.PMID:33929997DOI:10.1097/CAD.0000000000001073.
Bigelovin, a sesquiterpene lactone extracted from plant Inula helianthus aquatica, exhibited multiple interesting biological activities, including anti-inflammation, antiangiogenesis and cytotoxic action against cancer cells. In the present study, we found that Bigelovin reduced the viability of human colon cancer cells and induced their apoptosis in a time- and dose-dependent manner, with an IC50-5 μM. RNAseq and luciferase reporter analyses revealed that the nuclear factor kappa B (NF-κB) signaling was one of the most significantly inhibited pathways after Bigelovin treatment. Further systemic examination showed that exposure to Bigelovin resulted in ubiquitination and degradation of inhibitor of kappa-B kinase-beta (IKK-β) and decrease of IκB-α and p65 phosphorylation, which led to the downregulation of NF-κB-regulated genes expression. Moreover, enforced expression of exogenous IKK-β attenuated Bigelovin-induced NF-κB suppression and cell viability reduction. These results indicated that Bigelovin exerts a cytotoxic action against colon cancer cells through the induction of IKK-β degradation and consequently the inhibition of NF-κB signaling. Given the abnormal activation of NF-κB signaling in colorectal cancer (CRC) cells and the critical role of chronic inflammation in CRC development, it is conceivable that at least some colorectal cancer cells are addictive to NF-κB activation and targeting the pathway is an effective anti-CRC strategy.
Bigelovin inhibits STAT3 signaling by inactivating JAK2 and induces apoptosis in human cancer cells
Acta Pharmacol Sin 2015 Apr;36(4):507-16.PMID:25619393DOI:10.1038/aps.2014.143.
Aim: To study the function and mechanism of Bigelovin, a sesquiterpene lactone from the flower of Chinese herb Inula hupehensis, in regulating JAK2/STAT3 signaling and cancer cell growth. Methods: HepG2 cells stably transfected with the STAT3-responsive firefly luciferase reporter plasmid (HepG2/STAT3 cells), and a panel of human cancer cell lines were used to identify active compounds. Cell viability was measured using MTT assay. Western blotting was used to detect protein expression and phosphorylation. Kinase assays were performed and the reaction between Bigelovin and thiol-containing compounds was analyzed with LC-MS. Results: Bigelovin (1-50 μmol/L) dose-dependently inhibited the IL-6-induced STAT3 activation in HepG2/STAT3 cells (IC50=3.37 μmol/L) and the constitutive STAT3 activation in A549 and MDA-MB-468 cells. Furthermore, Bigelovin dose-dependently inhibited JAK2 phosphorylation in HeLa and MDA-MB-468 cells, as well as the enzymatic activity of JAK2 in vitro (IC50=44.24 μmol/L). Pretreatment of the cells with DTT (500 μmol/L) or GSH (500 μmol/L) eliminated the inhibitory effects of Bigelovin on the IL-6-induced and the constitutive STAT3 activation. The results in LC-MS analysis suggested that Bigelovin might react with cysteine residues of JAK2 leading to inactivation of JAK2. Bigelovin (5 and 20 μmol/L) had no effects on the signaling pathways of growth factors EGF, PDGF or insulin. Finally, Bigelovin suppressed the cell viability and induced apoptosis in 10 different human cancer cell lines, particularly those with constitutively activated STAT3. Conclusion: Bigelovin potently inhibits STAT3 signaling by inactivating JAK2, and induces apoptosis of a variety of human cancer cells in vitro.
Bigelovin triggered apoptosis in colorectal cancer in vitro and in vivo via upregulating death receptor 5 and reactive oxidative species
Sci Rep 2017 Feb 9;7:42176.PMID:28181527DOI:10.1038/srep42176.
Colorectal cancer (CRC) is the third most prevalent cancer and the third highest cancer-related mortality in the United States. Bigelovin, a sesquiterpene lactone isolated from Inula helianthus aquatica, has been proven to induce apoptosis and exhibit anti-inflammatory and anti-angiogenic activities. However, the effects of Bigelovin on CRC and underlying mechanisms have not been explored. The present study demonstrated that Bigelovin exhibited potent anti-tumor activities against CRC in vitro and in vivo. Bigelovin suppressed cell proliferation and colony formation and induced apoptosis in human colorectal cancer HT-29 and HCT 116 cells in vitro. Results also revealed that Bigelovin activated caspases, caused the G2/M cell cycle arrest and induced DNA damage through up-regulation of death receptor (DR) 5 and increase of ROS. In HCT 116 xenograft model, Bigelovin treatment resulted in suppression of tumor growth. Bigelovin at 20 mg/kg showed more significant tumor suppression and less side effects than conventional FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. In addition, in vivo data confirmed that anti-tumor activity of Bigelovin in CRC was through induction of apoptosis by up-regulating DR5 and increasing ROS. In conclusion, these results strongly suggested that Bigelovin has potential to be developed as therapeutic agent for CRC patients.
Bigelovin inhibits hepatocellular carcinoma cell growth and metastasis by regulating the MAPT-mediated Fas/FasL pathway
Neoplasma 2023 Feb 23;221125N1132.PMID:36812233DOI:10.4149/neo_2023_221125N1132.
Bigelovin (BigV), as traditional Chinese medicine, has been shown to inhibit the malignant progression of hepatocellular carcinoma (HCC). This study aimed to investigate whether BigV affects the development of HCC by targeting the MAPT and Fas/FasL pathway. Human HCC cell lines HepG2 and SMMC-7721 were used for this study. Cells were treated with BigV, sh-MAPT, and MAPT. The viability, migration, and apoptosis of HCC cells were detected by CCK-8, Transwell, and flow cytometry assays, respectively. Immunofluorescence and immunoprecipitation were used to verify the relationship between MAPT and Fas. Subcutaneous xenograft tumor and tail vein-injected lung metastases mouse models were constructed for histological observation. Hematoxylin-eosin staining was used to assess lung metastases in HCC. Western blotting was used to measure the expression of migration, apoptosis, and epithelial-mesenchymal transition (EMT) marker proteins, as well as Fas/FasL pathway-related proteins. BigV treatment inhibited the proliferation, migration, and EMT of HCC cells, whereas enhanced cell apoptosis. Moreover, BigV downregulated MAPT expression. The negative effects of sh-MAPT on HCC cell proliferation, migration, and EMT were enhanced by BigV treatment. Conversely, BigV addition attenuated the positive effects of MAPT overexpression on the malignant progression of HCC. In vivo experiments showed that BigV and/or sh-MAPT reduced tumor growth and lung metastasis while promoting tumor cell apoptosis. Furthermore, MAPT could act with Fas and inhibit its expression. sh-MAPT upregulated the expression of Fas/FasL pathway-associated proteins, which were enhanced by BigV administration. BigV suppressed the malignant progression of HCC via activating the MAPT-mediated Fas/FasL pathway.
Natural small molecule Bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/STAT3 pathway
Biochem Pharmacol 2018 Apr;150:191-201.PMID:29454618DOI:10.1016/j.bcp.2018.02.017.
Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after Bigelovin treatments. Results showed that Bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e.g. increased populations of T lymphocytes and macrophages) in orthotopic colon tumor allograft-bearing mice. Furthermore, the inhibitory activities were also validated in the experimental human colon cancer metastatic mouse model. The underlying mechanisms involved in the anti-metastatic effects of Bigelovin were then revealed in murine colon tumor cells colon 26-M01 and human colon cancer cells HCT116. Results showed that Bigelovin induced cytotoxicity, inhibition of cell proliferation, motility and migration in both cell lines, which were through interfering IL6/STAT3 and cofilin pathways. Alternations of the key molecules including Rock, FAK, RhoA, Rac1/2/3 and N-cadherin, which were detected in bigelovin-treated cancer cells, were also observed in the tumor allografts of bigelovin-treated mice. These findings strongly indicated that Bigelovin has potential to be developed as anti-tumor and anti-metastatic agent for colorectal cancer.