Cucurbitacin D
(Synonyms: 葫芦素 D) 目录号 : GC35757
A triterpenoid with diverse biological activities
Cas No.:3877-86-9
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
Cucurbitacin D is a triterpenoid that has been found in Cucurbita texana and has diverse biological activities.1,2,3 It decreases levels of the heat shock protein 90 (Hsp90) client proteins HER2, Raf, and cyclin-dependent kinase 6 (Cdk6) in MCF-7 breast cancer cell lysates in a concentration-dependent manner and inhibits the proliferation of MCF-7 cells (IC50 = 0.598 ?M).1 Cucurbitacin D (0.1 ?M) inhibits cigarette smoke condensate-induced HIV-1 replication in chronically HIV-1-infected U1 macrophages.2 In vivo, cucurbitacin D (0.025 mg/kg) decreases cold and mechanical allodynia in a mouse model of neuropathic pain induced by paclitaxel .3
1.Hall, J.A., Seedarala, S., Rice, N., et al.Cucurbitacin D Is a disruptor of the HSP90 chaperone machineryJ. Nat. Prod.78(4)873-879(2015) 2.Kodidela, S., Sinha, N., Kumar, A., et al.Anti-HIV activity of cucurbitacin-D against cigarette smoke condensate-induced HIV replication in the U1 macrophagesViruses13(6)1004(2021) 3.Lee, J.H., Kim, B., Ko, S.-G., et al.Analgesic effect of SH003 and Trichosanthes kirilowii Maximowicz in paclitaxel-induced neuropathic pain in miceCurr. Issues Mol. Biol.44(2)718-730(2022)
| Cas No. | 3877-86-9 | SDF | |
| 别名 | 葫芦素 D | ||
| Canonical SMILES | C[C@@]([C@@](CC=C(C(C)1C)[C@@]2([H])C[C@H](O)C1=O)([H])[C@@]2(C)C3=O)(C[C@@H](O)[C@]4([H])[C@@](C)(O)C(/C=C/C(C)(O)C)=O)[C@@]4(C3)C | ||
| 分子式 | C30H44O7 | 分子量 | 516.67 |
| 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 | 1.9355 mL | 9.6774 mL | 19.3547 mL |
| 5 mM | 0.3871 mL | 1.9355 mL | 3.8709 mL |
| 10 mM | 0.1935 mL | 0.9677 mL | 1.9355 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。
Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
Cancers (Basel) 2019 Mar 14;11(3):364.PMID:30875788DOI:10.3390/cancers11030364.
Prostate cancer (PrCa) metastasis is the major cause of mortality and morbidity among men. Metastatic PrCa cells are typically adopted for aberrant glucose metabolism. Thus, chemophores that reprogram altered glucose metabolic machinery in cancer cells can be useful agent for the repression of PrCa metastasis. Herein, we report that Cucurbitacin D (Cuc D) effectively inhibits glucose uptake and lactate production in metastatic PrCa cells via modulating glucose metabolism. This metabolic shift by Cuc D was correlated with decreased expression of GLUT1 by its direct binding as suggested by its proficient molecular docking (binding energy -8.5 kcal/mol). Cuc D treatment also altered the expression of key oncogenic proteins and miR-132 that are known to be involved in glucose metabolism. Cuc D (0.1 to 1 µM) treatment inhibited tumorigenic and metastatic potential of human PrCa cells via inducing apoptosis and cell cycle arrest in G2/M phase. Cuc D treatment also showed inhibition of tumor growth in PrCa xenograft mouse model with concomitant decrease in the expression of GLUT1, PCNA and restoration of miR-132. These results suggest that Cuc D is a novel modulator of glucose metabolism and could be a promising therapeutic modality for the attenuation of PrCa metastasis.
Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer
Sci Rep 2016 Nov 8;6:36594.PMID:27824155DOI:10.1038/srep36594.
In this study, we for the first time, investigated the potential anti-cancer effects of a novel analogue of cucurbitacin (Cucurbitacin D) against cervical cancer in vitro and in vivo. Cucurbitacin D inhibited viability and growth of cervical cancer cells (CaSki and SiHa) in a dose-dependent manner. IC50 of Cucurbitacin D was recorded at 400 nM and 250 nM in CaSki and SiHa cells, respectively. Induction of apoptosis was observed in Cucurbitacin D treated cervical cancer cells as measured by enhanced Annexin V staining and cleavage in PARP protein. Cucurbitacin D treatment of cervical cancer cells arrested the cell cycle in G1/S phase, inhibited constitutive expression of E6, Cyclin D1, CDK4, pRb, and Rb and induced the protein levels of p21 and p27. Cucurbitacin D also inhibited phosphorylation of STAT3 at Ser727 and Tyr705 residues as well as its downstream target genes c-Myc, and MMP9. Cucurbitacin D enhanced the expression of tumor suppressor microRNAs (miR-145, miRNA-143, and miRNA34a) in cervical cancer cells. Cucurbitacin D treatment (1 mg/kg body weight) effectively inhibited growth of cervical cancer cells derived orthotopic xenograft tumors in athymic nude mice. These results demonstrate the potential therapeutic efficacy of Cucurbitacin D against cervical cancer.
Cucurbitacin D Inhibits the Proliferation of HepG2 Cells and Induces Apoptosis by Modulating JAK/STAT3, PI3K/Akt/mTOR and MAPK Signaling Pathways
Curr Cancer Drug Targets 2022;22(11):931-944.PMID:35786188DOI:10.2174/1568009622666220623141158.
Background: Cucurbitacin D (CuD) is a natural compound that can be isolated in various plant families, mainly from Ecballium elaterium (L.) A. Rich. (E. elaterium). It is a triterpenoid with a broad spectrum of biological activity, including anti-cancer properties. Hepatocellular carcinoma, the aggressive type of liver cancer, is an important public health problem worldwide. Objective: In the present study, we investigated the anticancer effect of CuD treated at different doses on the HepG2 cell line and the underlying mechanism in vitro. Methods: CuD was isolated from the fruit juice of E. elaterium plant, and quantitative analysis was performed using high-performance liquid chromatography. The cell viability effect of purified CuD was determined by the MTT test, and also cell apoptosis and cell cycle arrest effects were determined by flow cytometry. DNA damage was evaluated with the comet test. Proteins and genes involved in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 signaling pathways were evaluated by western blot and qRT-PCR. Results: CuD showed both antiproliferative and cytotoxic effects against the HepG2 cell line in a dose and time-dependent manner. It was observed that CuD induced apoptosis and blocked the cell cycle in HepG2 cells. It was observed that the expressions of genes and some proteins that play a key role in PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades were dose-dependently downregulated and led to activatation of the apoptotic pathway. Conclusion: All these results show promise that CuD may have a therapeutic effect in hepatocellular carcinoma.
Cucurbitacin D is a new inflammasome activator in macrophages
Int Immunopharmacol 2013 Dec;17(4):1044-50.PMID:24140411DOI:10.1016/j.intimp.2013.10.003.
We previously reported that Cucurbitacin D isolated from Trichosanthes kirilowii has anti-tumor roles to leukemia cells. However, the effect of Cucurbitacin D on immune cells is not fully understood although there is no toxic activity to normal cells. In this study, immunomodulating activities of Cucurbitacin D were investigated in macrophages. Cucurbitacin D could increase LPS-induced interleukin (IL)-1β production in culture supernatant of THP-1 cells, peritoneal exudate cells (PECs), bone marrow derived macrophages (BMDMs), and RAW264 cells. At the transcriptional level, Cucurbitacin D enhanced LPS-induced IL-1β mRNA expression through activation of ERK1/2 mitogen-activated protein kinases (MAPKs). At the posttranscriptional level, the activation of caspase-1 induced by Cucurbitacin D has also been demonstrated following treatment with a caspase-1 inhibitor and siRNA. Importantly, Cucurbitacin D has further been shown to induce inflammasome activation independent of ERK1/2 activation. Western blotting showed interaction of NOD-like receptor family, pyrin domain containing 3 (NALP3) and apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain (ASC), suggesting activation of the inflammasome and a possible reason for activation of caspase-1. Taken together, these results suggest that Cucurbitacin D could initiate immunomodulating activity in macrophages to lead to inflammasome activation as well as enhancement of LPS signaling.
Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery
J Nat Prod 2015 Apr 24;78(4):873-9.PMID:25756299DOI:10.1021/acs.jnatprod.5b00054.
Heat shock protein 90 (Hsp90) facilitates the maturation of many newly synthesized and unfolded proteins (clients) via the Hsp90 chaperone cycle, in which Hsp90 forms a heteroprotein complex and relies upon cochaperones, immunophilins, etc., for assistance in client folding. Hsp90 inhibition has emerged as a strategy for anticancer therapies due to the involvement of clients in many oncogenic pathways. Inhibition of chaperone function results in client ubiquitinylation and degradation via the proteasome, ultimately leading to tumor digression. Small molecule inhibitors perturb ATPase activity at the N-terminus and include derivatives of the natural product geldanamycin. However, N-terminal inhibition also leads to induction of the pro-survival heat shock response (HSR), in which displacement of the Hsp90-bound transcription factor, heat shock factor-1, translocates to the nucleus and induces transcription of heat shock proteins, including Hsp90. An alternative strategy for Hsp90 inhibition is disruption of the Hsp90 heteroprotein complex. Disruption of the Hsp90 heteroprotein complex is an effective strategy to prevent client maturation without induction of the HSR. Cucurbitacin D, isolated from Cucurbita texana, and 3-epi-isocucurbitacin D prevented client maturation without induction of the HSR. Cucurbitacin D also disrupted interactions between Hsp90 and two cochaperones, Cdc37 and p23.