Arenobufagin
(Synonyms: 沙蟾毒精) 目录号 : GC32837
A cardiotonic steroid with anticancer activity
Cas No.:464-74-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Arenobufagin is a cardiotonic steroid that has been found in the skin secretions of the toad B. gargarizans and has anticancer activity.1,2,3,4 It inhibits Na+/K+-ATPase activity in isolated guinea pig ventricular myocytes with an IC50 value of 290 nM.1 Arenobufagin (20-500 nM) induces cleavage of poly(ADP-ribose) polymerase (PARP), caspase-3, and caspase-9, as well as induces apoptosis in HepG2 hepatocellular carcinoma cells.2 It inhibits proliferation of HepG2, Hep3B, BEL-7402, and MCF-7 cancer cells (IC50s = 101.9, 39.8, 416.3, and 143.7 nM, respectively), as well as multidrug-resistant HepG2/adm and MCF-7/adr cancer cells (IC50s = 730 and 67.5 nM, respectively). Arenobufagin (1 mg/kg once per day, i.v.) reduces tumor growth, the number and size of lung metastases, and tumor levels of the epithelial-to-mesenchymal transition (EMT) markers vimentin and β-catenin in a PC3 mouse xenograft model.3 Arenobufagin (5 and 10 ?M/plug) inhibits VEGF-induced angiogenesis in a Matrigel? plug assay in mice.4
1.dos Santos Cruz, J., and Matsuda, H.Arenobufagin, a compound in toad venom, blocks Na+-K+ pump current in cardiac myocytesEur. J. Pharmacol.239(1-3)223-226(1993) 2.Zhang, D.-M., Liu, J.-S., Deng, L.-J., et al.Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/ mTOR pathwayCarcinogenesis34(6)1331-1342(2013) 3.Chen, L., Mai, W., Chen, M., et al.Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating β-cateninPharmacol. Res.123130-142(2017) 4.Li, M.W., S., Liu, Z., Zhang, W., et al.Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathwayBiochem. Pharmacol.83(9)1251-1260(2012)
| Cas No. | 464-74-4 | SDF | |
| 别名 | 沙蟾毒精 | ||
| Canonical SMILES | C[C@]([C@@H](C(C=C1)=COC1=O)CC2)(C3=O)[C@]2([C@@](CC[C@@]4([H])[C@@]5(CC[C@H](O)C4)C)([H])[C@]5([H])[C@@H]3O)O | ||
| 分子式 | C24H32O6 | 分子量 | 416.51 |
| 溶解度 | Ethanol : 10 mg/mL (24.01 mM) | 储存条件 | Store at 2-8°C |
| 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 | 2.4009 mL | 12.0045 mL | 24.009 mL |
| 5 mM | 0.4802 mL | 2.4009 mL | 4.8018 mL |
| 10 mM | 0.2401 mL | 1.2005 mL | 2.4009 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。
Arenobufagin intercalates with DNA leading to G2 cell cycle arrest via ATM/ATR pathway
Oncotarget 2015 Oct 27;6(33):34258-75.PMID:26485758DOI:10.18632/oncotarget.5545.
Arenobufagin, a representative bufadienolide, is the major active component in the traditional Chinese medicine Chan'su. It possesses significant antineoplastic activity in vitro. Although bufadienolide has been found to disrupt the cell cycle, the underlying mechanisms of this disruption are not defined. Here, we reported that Arenobufagin blocked the transition from G2 to M phase of cell cycle through inhibiting the activation of CDK1-Cyclin B1 complex; The tumor suppressor p53 contributed to sustaining arrest at the G2 phase of the cell cycle in hepatocellular carcinoma (HCC) cells. Moreover, Arenobufagin caused double-strand DNA breaks (DSBs) and triggered the DNA damage response (DDR), partly via the ATM/ATR-Chk1/Chk2-Cdc25C signaling pathway. Importantly, we used a synthetic biotinylated arenobufagin-conjugated chemical probe in live cells to show that Arenobufagin accumulated mainly in the nucleus. The microscopic thermodynamic parameters measured using isothermal titration calorimetry (ITC) also demonstrated that Arenobufagin directly bound to DNA in vitro. The hypochromicity in the UV-visible absorption spectrum, the significant changes in the circular dichroism (CD) spectrum of DNA, and the distinct quenching in the fluorescence intensity of the ethidium bromide (EB)-DNA system before and after Arenobufagin treatment indicated that Arenobufagin bound to DNA in vitro by intercalation. Molecular modeling suggested Arenobufagin intercalated with DNA via hydrogen bonds between Arenobufagin and GT base pairs. Collectively, these data provide novel insights into arenobufagin-induced cell cycle disruption that are valuable for the further discussion and investigation of the use of Arenobufagin in clinical anticancer chemotherapy.
Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway
Molecules 2017 Sep 11;22(9):1525.PMID:28892004DOI:10.3390/molecules22091525.
Arenobufagin, an active component isolated from the traditional Chinese medicine Chan Su, exhibits anticancer influences in several human malignancies. However, the effects and action mechanisms of Arenobufagin on non-small-cell lung cancer (NSCLC) are still unknown. In this study, we reported that Arenobufagin acted through activation of Noxa-related pathways and promoted apoptotic cell death in human NSCLC cells. Our results revealed that arenobufagin-induced apoptosis was caspase-dependent, as evidenced by the fact that caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP) were cleaved, and pretreatment with a pan-caspase inhibitor Z-VAD-FMK inhibited the pro-apoptosis effect of Arenobufagin. Mechanistically, we further found that Arenobufagin rapidly upregulated the expression of the pro-apoptosis protein Noxa, and abrogated the anti-apoptosis protein Mcl-1, a major binding partner of Noxa in the cell. More importantly, the knockdown of Noxa greatly blocked arenobufagin-induced cell death, highlighting the contribution of this protein in the anti-NSCLC effects of Arenobufagin. Interestingly, Arenobufagin also increased the expression of p53, a direct transcriptional activator for the upregulation of the Noxa protein. Taken together, our results suggest that Arenobufagin is a potential anti-NSCLC agent that triggers apoptotic cell death in NSCLC cells through interfering with the Noxa-related pathway.
Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating β-catenin
Pharmacol Res 2017 Sep;123:130-142.PMID:28712972DOI:10.1016/j.phrs.2017.07.009.
Epithelial-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis; thus, developing EMT inhibitors may be a feasible treatment for metastatic PCa. Here, we discovered that Arenobufagin and four other bufadienolides suppressed PC3 cell EMT. These compounds modulated EMT marker expression with elevating E-cadherin and reducing ZEB1, vimentin and slug expression, and attenuated the migration and invasion of PC3 cells. Among these five compounds, Arenobufagin exhibited the most potent activity. We found that the mRNA and protein expression of β-catenin and β-catenin/TCF4 target genes, which are related to tumor invasion and metastasis, were down-regulated after Arenobufagin treatment. Overexpression of β-catenin in PC3 cells antagonized the EMT inhibition effect of Arenobufagin, while silencing β-catenin with siRNA enhanced the inhibitory effect of Arenobufagin on EMT. In addition, Arenobufagin restrained xenograft tumor EMT, as demonstrated by decreased mesenchymal marker expression and increased epithelial marker expression, and reduced the tumor metastatic foci in lung. This study demonstrates a novel anticancer activity of Arenobufagin, which inhibits PC3 cell EMT by down-regulating β-catenin, thereby reducing PCa metastasis. In addition, it also provides new evidence for the development of Arenobufagin as a treatment for metastatic prostate cancer.
Discovery of 3-peptide substituted Arenobufagin derivatives as potent antitumor agents with low cardiotoxicity
Steroids 2021 Feb;166:108772.PMID:33271132DOI:10.1016/j.steroids.2020.108772.
Active natural productscan be valuable lead compounds and numerous drugs derived from natural products have successfully entered the clinic. Arenobufagin, one of the important active components of toad venom, indicates significant antitumor activities with limited preclinical development for its strong cardiotoxicity. Ten 3-monopeptide substituted Arenobufagin derivatives have been designed and synthesized. Antitumor activity and cardiotoxicity assays lead to the discovery of compound ZM226 as a potent antitumor agent with low cardiotoxicity. These findings suggest optimization of Arenobufagin on position 3 maybe an efficacious strategy for the development of antitumor drug candidates derived from Arenobufagin.
Arenobufagin Inhibits the Phosphatidylinositol 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin Pathway and Induces Apoptosis and Autophagy in Pancreatic Cancer Cells
Pancreas 2020 Feb;49(2):261-272.PMID:32011523DOI:10.1097/MPA.0000000000001471.
Objective: The aim of the study was to investigate the effects of Arenobufagin on pancreatic carcinoma in vitro and in vivo and its molecular mechanism. Methods: The proliferation of pancreatic cancer cells was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Transmission electron microscopy was used to observe the formation of autophagic vacuoles after Arenobufagin treatment. Hoechst 33258 and monodansylcadaverine fluorescence staining were performed to evaluate cell apoptosis and autophagy. Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and JC-1 staining assays were used to evaluate apoptosis-related changes. Reverse-transcription polymerase chain reaction and western blotting were carried out to examine the expression of apoptosis- and autophagy-related markers after Arenobufagin treatment. A tumor xenograft nude mouse model was established to evaluate Arenobufagin efficacy in vivo. Results: Arenobufagin effectively inhibited the proliferation of SW1990 and BxPC3 cells and induced cell arrest, apoptosis, and autophagy. Arenobufagin upregulated the expression of apoptotic- and autophagy-related proteins while downregulated the expression of phosphatidylinositol 3-kinase family proteins. Furthermore, Arenobufagin also exerted inhibitory effects on tumor growth in xenograft nude mice. Conclusions: Arenobufagin inhibits tumor growth in vivo and in vitro. The mechanism underlying Arenobufagin action may involve induction of autophagy and apoptosis through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway.