Ethoxysanguinarine
(Synonyms: 乙氧基血根碱) 目录号 : GC38083
Ethoxysanguinarine 是主要存在龙葵中的一种 benzophenanthridine 生物碱天然产物。Ethoxysanguinarine 通过抑制蛋白磷酸酶 2A (CIP2A)，抑制结直肠癌细胞的活力，诱导细胞凋亡。
Cas No.:28342-31-6
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
Ethoxysanguinarine is a benzophenanthridine alkaloid natural product that is mainly found in Macleaya cordata. Ethoxysanguinarine inhibits viability and induces apoptosis of colorectal cancer cells by inhibiting protein phosphatase 2A (CIP2A)[1].
[1]. Jin L, et al. Ethoxysanguinarine inhibits viability and induces apoptosis of colorectal cancer cells by inhibiting CIP2A. Int J Oncol. 2018 Mar 16.
| Cas No. | 28342-31-6 | SDF | |
| 别名 | 乙氧基血根碱 | ||
| Canonical SMILES | CN1C2=C3C(C=C4OCOC4=C3)=CC=C2C5=C(C6=C(OCO6)C=C5)C1OCC | ||
| 分子式 | C22H19NO5 | 分子量 | 377.39 |
| 溶解度 | Soluble in DMSO | 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 | 2.6498 mL | 13.2489 mL | 26.4978 mL |
| 5 mM | 0.53 mL | 2.6498 mL | 5.2996 mL |
| 10 mM | 0.265 mL | 1.3249 mL | 2.6498 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。
[Ethoxysanguinarine directly targets CIP2A to inhibit proliferation and induce autophagy of SGC7901/DDP cells]
Zhongguo Zhong Yao Za Zhi 2022 Nov;47(21):5890-5899.PMID:36472008DOI:10.19540/j.cnki.cjcmm.20220706.701.
This study aims to investigate the effect of Ethoxysanguinarine(Eth) on cisplatin(DDP)-resistant human gastric cancer cells and decipher the underlying mechanism. The human gastric cancer cell line SGC7901 and the DDP-resistant cell line SGC7901/DDP were used as the cell models. Western blot was employed to determine the expression levels of multidrug resistance-related proteins, and methyl thiazolyl tetrazolium(MTT) assay to detect the proliferation of SGC7901 and SGC7901/DDP cells exposed to DDP. After treatment with different concentrations of Eth, the proliferation of SGC7901 and SGC7901/DDP cells was detected by MTT assay, trypan blue exclusion assay, colony formation assay, and high-content imaging and analysis system. The apoptosis of SGC7901/DDP cells was detected by flow cytometry with Annexin V-FITC/PI staining. GFP-LC3 transfection was carried out to detect the effect of Eth on the autophagy of SGC7901/DDP cells. The expression levels of the multidrug resistance-related protein P-glycoprotein(P-gp), the apoptosis-related proteins [caspase-9, caspase-3, and poly(ADP-ribose) polymerase(PARP)], the autophagy-related protein light chain 3-Ⅱ(LC3-Ⅱ), the key effectors [mammalian target of rapamycin(mTOR), 70 kDa ribosomal protein S6 kinase(P70 S6 K), and 4 E binding protein 1(4 E-BP1)] of the mammalian target of rapamycin complex 1(mTORC1) signaling pathway, cancerous inhibitor of protein phosphatase 2A(CIP2A), and protein kinase B(Akt) were measured by Western blot. The mRNA level of CIP2A in the SGC7901/DDP cells exposed to Eth for 24 h was analyzed by RT-qPCR. After SGC7901/DDP cells were transfected with CIP2A expression vector pcDNA3.1-HA-CIP2A and treated with different concentrations of Eth, MTT assay was used to determine the prolife-ration of SGC7901/DDP cells and Western blot to detect the expression levels of related proteins. The interaction sites of Eth and CIP2A were predicted by molecular docking. The affinity between Eth and CIP2A was determined by drug affinity responsive target stability(DARTS) assay. The pharmacokinetic properties and drug-like activity of Eth were predicted by SwissADME. The results indicated that SGC7901/DDP cells were more sensitive to Eth than SGC7901 cells. Eth significantly inhibited proliferation and colony formation and changed the morphology, roundness, and area of SGC7901/DDP cells. Eth treatment caused the nucleus shrinking and significantly increased the apoptosis rate of the cells. Furthermore, Eth down-regulated the expression of caspase-9 and caspase-3 precursors and promoted the cleavage of PARP, which suggested that Eth induced the apoptosis of SGC7901/DDP cells. The GFP-LC3 in Eth-treated cells showed speckled aggregation. The up-regulated expression of LC3-Ⅱ by Eth indicated that Eth activated the autophagy of SGC7901/DDP cells. Eth down-regulated the expression of P-gp, the phosphorylation of mTOR, P70 S6K, and 4E-BP1, the expression of CIP2A, and the phosphorylation of Akt. Additionally, it increased the activity of PP2A, and had no significant effect on the expression of CIP2A in SGC7901/DDP cells. CIP2A overexpression antagonized the inhibition of cell proliferation and the activation of autophagy by Eth. Molecular docking suggested that Eth bound to CIP2A. The results of DARTS assay further proved the above binding effect. Eth has potential drug-like activity. The above results demonstrated that Eth inhibited the proliferation, induced the apoptosis, and activated the autophagy of SGC7901/DDP cells by targeting CIP2A and then down-regulating PP2A/mTORC1 signaling pathway. This study provided a new target for the treatment of cisplatin-resistant gastric cancer.
Ethoxysanguinarine inhibits viability and induces apoptosis of colorectal cancer cells by inhibiting CIP2A
Int J Oncol 2018 May;52(5):1569-1578.PMID:29568959DOI:10.3892/ijo.2018.4323.
Cancerous inhibitor of protein phosphatase 2A (CIP2A) an endogenous inhibitor of protein phosphatase 2A (PP2A), which can promote proliferation and transformation of several cancer types, has been shown to be a target for tumor therapy. The present study investigated the effects and underlying mechanisms of action of a novel natural compound, Ethoxysanguinarine (Eth), on colorectal cancer (CRC) cells. MTT assay and flow cytometric assay found that Eth inhibited the viability and induced the apoptosis of the CRC cells. The inhibition of viability and activation of apoptosis was mediated through the Eth-induced decrease in CIP2A expression. Knockdown of CIP2A by RNA interference sensitized, whereas overexpression of CIP2A antagonized, Eth-induced viability inhibition and apoptosis. Furthermore, western blot analysis suggested that Eth inhibited phosphorylation of CIP2A downstream molecule protein kinase B via the activation of PP2A. CRC xenograft tests also confirmed the antitumor effect of Eth in vivo. These results advance our understanding of Eth-induced viability inhibition and apoptosis, implying the requirement for further investigation of Eth as a CIP2A inhibitor for cancer therapies.
Ethoxysanguinarine, a Novel Direct Activator of AMP-Activated Protein Kinase, Induces Autophagy and Exhibits Therapeutic Potential in Breast Cancer Cells
Front Pharmacol 2020 Jan 8;10:1503.PMID:31969821DOI:10.3389/fphar.2019.01503.
Ethoxysanguinarine (Eth) is a benzophenanthridine alkaloid extracted from Macleaya cordata (Willd) R. Br. It possesses antibacterial and antiviral activities and offers therapeutic benefits for the treatment of respiratory syndrome virus-induced cytopathic effects. However, the effect of Eth on human tumors and its pharmacological effects remain to be elucidated, together with its cellular target. Here, we examined the effects of Eth on breast cancer (BC) cells. We found that at low doses, Eth strongly inhibited the viability of BC cell lines and induced autophagy. Mechanistic studies showed that Eth induced autophagy by upregulating the activity of the AMP-activated protein kinase (AMPK). The AMPK inhibitor compound C significantly attenuated Eth-induced autophagy and inhibited proliferation. Meanwhile, the AMPK activator metformin significantly enhanced Eth-induced autophagy and inhibited proliferation. Computational docking and affinity assays showed that Eth directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. AMPK was less activated in tumor samples compared to normal breast tissues and was inversely associated with the prognosis of the patients. Moreover, Eth exhibited potent anti-BC activity in nude mice and favorable pharmacokinetics in rats. These characteristics render Eth as a promising candidate drug for further development and for designing new effective AMPK activators.
Ethoxysanguinarine Induces Inhibitory Effects and Downregulates CIP2A in Lung Cancer Cells
ACS Med Chem Lett 2013 Dec 20;5(2):113-8.PMID:24900782DOI:10.1021/ml400341k.
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is able to stabilize c-Myc oncogenic transcription factor and promote proliferation and transformation of cells. CIP2A is overexpressed in many primary tumors, and pharmacological inactivation of CIP2A is an emerging concept for the development of novel anticancer agents. In this study, we demonstrate that overexpression of CIP2A predicts poor prognosis in lung cancer, and a natural compound, Ethoxysanguinarine (ESG), effectively downregulates CIP2A protein and its downstream signaling molecules, c-Myc and pAkt, and induces protein phosphatase 2A (PP2A) activity. ESG inhibits proliferation and induces apoptosis of lung cancer cells, and enhances the effects of cisplatin on malignant cells. Taken together, our findings demonstrate that CIP2A is inversely associated with the clinical outcome of lung cancer, and ESG can serve as a lead compound for the development of CIP2A inhibitor for cancer therapies.
Ethoxysanguinarine Induces Apoptosis, Inhibits Metastasis and Sensitizes cells to Docetaxel in Breast Cancer Cells through Inhibition of Hakai
Chem Biodivers 2023 Feb;20(2):e202200284.PMID:36633334DOI:10.1002/cbdv.202200284.
Ethoxysanguinarine (ESG) is a benzophenanthridine alkaloid extracted from plants of Papaveraceae family, such as Macleaya cordata (Willd) R. Br. The anti-cancer activity of ESG has been rarely reported. In this study, we investigated the anti-breast cancer effect of ESG and its underlying mechanism. MTT assay and flow cytometry analysis showed that ESG inhibited the viability and induced apoptosis in MCF7 and MDA-MB-231 human breast cancer cells. Western blot revealed that ESG triggered intrinsic and extrinsic apoptotic pathways, as evidenced by the activation of caspase-8, caspase-9 and caspase-3. ESG attenuated breast cancer cell migration and invasion through Hakai/E-cadherin/N-cadherin. Moreover, Hakai knockdown sensitized ESG-triggered viability and motility inhibition, suggesting that Hakai mediated the anti-breast cancer effect of ESG. In addition, ESG potentiated the anti-cancer activity of docetaxel (DTX) in breast cancer cells. Overall, our findings demonstrate that ESG exhibits outstanding pro-apoptosis and anti-metastasis effects on breast cancer via a mechanism related to Hakai-related signaling pathway.