Proscillaridin A
(Synonyms: 原海葱甙A) 目录号 : GC39425
Proscillaridin A 是强力的拓扑异构酶 I 和 II topoisomerase I/II 抑制剂，抑制拓扑异构酶 I 和 II 的 IC50 值分别为 30 nM 和 100 nM。
Cas No.:466-06-8
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
Proscillaridin A is a potent poison of topoisomerase I/II activity with IC50 values of 30 nM and 100 nM, respectively[1].
[1]. Bielawski K, et al. Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin A.Biol Pharm Bull. 2006 Jul;29(7):1493-7.
| Cas No. | 466-06-8 | SDF | |
| 别名 | 原海葱甙A | ||
| Canonical SMILES | O[C@@]([C@@]1(CC2)C)(CC[C@@H]1C(C=C3)=COC3=O)[C@@](CCC4=C[C@@H](O[C@@](O[C@@H](C)[C@H](O)[C@H]5O)([H])[C@@H]5O)CC6)([H])[C@@]2([H])[C@]46C | ||
| 分子式 | C30H42O8 | 分子量 | 530.65 |
| 溶解度 | DMSO: 100 mg/mL (188.45 mM) | 储存条件 | Store at -20°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 | 1.8845 mL | 9.4224 mL | 18.8448 mL |
| 5 mM | 0.3769 mL | 1.8845 mL | 3.769 mL |
| 10 mM | 0.1884 mL | 0.9422 mL | 1.8845 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。
Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death
Int J Mol Sci 2022 Jun 23;23(13):6973.PMID:35805980DOI:10.3390/ijms23136973.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, Proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, Proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, Proscillaridin A enhanced TRAIL-induced cell death partly via O-glycosylation. Taken together, our findings suggest that Proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.
Repurposing Proscillaridin A in combination with decitabine against embryonal rhabdomyosarcoma RD cells
Cancer Chemother Pharmacol 2021 Nov;88(5):845-856.PMID:34331108DOI:10.1007/s00280-021-04339-6.
Purpose: Embryonal rhabdomyosarcoma (eRMS) is the most common type of rhabdomyosarcoma in children. eRMS is characterized by malignant skeletal muscle cells driven by hyperactivation of several oncogenic pathways including the MYC pathway. Targeting MYC in cancer has been extremely challenging. Recently, we have demonstrated that the heart failure drug, Proscillaridin A, produced anticancer effects with specificity toward MYC expressing leukemia cells. We also reported that decitabine, a hypomethylating drug, synergizes with Proscillaridin A in colon cancer cells. Here, we investigated whether Proscillaridin A exhibits epigenetic and anticancer activity against eRMS RD cells, overexpressing MYC oncogene, and its combination with decitabine. Methods: We investigated the anticancer effects of Proscillaridin A in eRMS RD cells in vitro. In response to drug treatment, we measured growth inhibition, cell cycle arrest, loss of clonogenicity and self-renewal capacity. We further evaluated the impact of Proscillaridin A on MYC expression and its downstream transcriptomic effects by RNA sequencing. Then, we measured protein expression of epigenetic regulators and their associated chromatin post-translational modifications in response to drug treatment. Chromatin immunoprecipitation sequencing data sets were coupled with transcriptomic results to pinpoint the impact of Proscillaridin A on gene pathways associated with specific chromatin modifications. Lastly, we evaluated the effect of the combination of Proscillaridin A and the DNA demethylating drug decitabine on eRMS RD cell growth and clonogenic potential. Results: Clinically relevant concentration of Proscillaridin A (5 nM) produced growth inhibition, cell cycle arrest and loss of clonogenicity in eRMS RD cells. Proscillaridin A produced a significant downregulation of MYC protein expression and inhibition of oncogenic transcriptional programs controlled by MYC, involved in cell replication. Interestingly, significant reduction in total histone 3 acetylation and on specific lysine residues (lysine 9, 14, 18, and 27 on histone 3) was associated with significant protein downregulation of a series of lysine acetyltransferases (KAT3A, KAT3B, KAT2A, KAT2B, and KAT5). In addition, Proscillaridin A produced synergistic growth inhibition and loss of clonogenicity when combined with the approved DNA demethylating drug decitabine. Conclusion: Proscillaridin A produces anticancer and epigenetic effects in the low nanomolar range and its combination with decitabine warrants further investigation for the treatment of eRMS.
Proscillaridin A induces apoptosis and inhibits the metastasis of osteosarcoma in vitro and in vivo
Biochem Biophys Res Commun 2020 Jan 22;521(4):880-886.PMID:31708095DOI:10.1016/j.bbrc.2019.11.012.
The side effects of chemotherapy, drug resistance, and tumor metastasis hinder the development of treatment for osteosarcoma, leading to poor prognosis of patients with the disease. Proscillaridin A, a kind of cardiac glycoside, has been proven to have anti-proliferative properties in many malignant tumors, but the efficacy of the drug in treating osteosarcoma is unclear. In the present study, we assessed the effects of Proscillaridin A on osteosarcoma and investigated its underlying action mechanism. The cell cytotoxicity assay showed that Proscillaridin A significantly inhibited the proliferation of 143B cells in a dose- and time-dependent manner. Also, flow cytometry and invasion assay revealed that Proscillaridin A induced apoptosis and reduced 143B cell motility. Western blotting and PCR were used to detect the expressions of Bcl-xl and MMP2 and showed that mRNA/protein expression levels decreased significantly in Proscillaridin A-treated osteosarcoma cells. Using a mouse xenograft model, we found that Proscillaridin A treatment significantly inhibited tumor growth and lung metastasis in vivo and decreased the expression levels of Bcl-xl and MMP2. No noticeable side effect was observed in the liver, kidney, and hematological functions. Conclusively, Proscillaridin A suppressed proliferation, induced apoptosis, and inhibited 143B cell metastasis in vitro and in vivo, and these effects could be mediated by downregulating the expressions of Bcl-xl and MMP2.
Proscillaridin A induces mitochondrial damage and autophagy in pancreatic cancer and reduces the stability of SMAD4 in Panc-1 cells
Ann Transl Med 2022 Aug;10(15):820.PMID:36034984DOI:10.21037/atm-22-1085.
Background: Pancreatic cancer (PC) is a highly metastatic and lethal cancer with a very low overall 5-year survival rate. There is an urgent need for identifying new therapeutic agents for this deadly disease. Cardiac glycosides (CGs) have been traditionally used for their potent cardiovascular activities and have also recently been reported to exhibit anti-tumor effects. Proscillaridin A (Pro A), a natural CG, has been shown to display anti-tumor effects on multiple cancer types. Methods: The cytotoxic effect of Pro A on PC cells was determined using cell viability assay, colony formation assay and transwell assay in vitro. Cell apoptosis, cell cycle, reactive oxygen species (ROS) generation, intracellular Ca2+ levels and mitochondrial membrane potential (MMP) were assayed by flow cytometry. Panc-1-xenografted mice model was used to evaluate Pro A's effect in tumor growth. Mitochondria morphology was observed by transmission electron microscopy. LC3 aggregation was assessed by GFP-LC3 fluorescence microscopy. Gene expression was assayed by western blot or real-time quantitative polymerase chain reaction (qPCR). Results: Pro A inhibits the proliferation, migration and invasion of Panc-1, BxPC-3 and AsPC-1 PC cells in vitro, and Panc-1 cells display the highest sensitivity with an IC50 at the nano-molar level. In vivo, Pro A treatment inhibits tumor progression in Panc-1 xenograft nude mice. Pro A treatment promotes both cell apoptosis and autophagy, and Pro A-treated PC cells display characteristics of mitochondrial damage including increased ROS generation, intracellular Ca2+ levels and disruption of MMP. In addition, high sensitivity towards Pro A of Panc-1 cells compared to BxPC-3 and AsPC-1 cells could be partially attributed to the loss of endogenous SMAD4 expression in the latter. Conclusions: Our findings suggest that Pro A constitutes a promising therapeutic candidate for certain types of PC.
Proscillaridin A inhibits hepatocellular carcinoma progression through inducing mitochondrial damage and autophagy
Acta Biochim Biophys Sin (Shanghai) 2021 Jan 12;53(1):19-28.PMID:33201987DOI:10.1093/abbs/gmaa139.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. At present, drug options for systemic treatment of HCC are very limited. There is an urgent need to develop additional effective drugs for HCC treatment. In the present study, we found that Proscillaridin A (ProA), a cardiac glycoside, exerted a strong anticancer effect on multiple HCC cell lines. ProA significantly inhibited the cell proliferation, migration, and invasion of HCC cells. ProA also had a marked inhibitory effect on the progression of HCC in the MHCC97H xenograft nude mouse model. ProA-mediated suppression of HCC was closely related to cell apoptosis. ProA-treated HCC cells displayed significant mitochondrial damage and elevated reactive oxygen species production, resulting in profound cell apoptosis. Meanwhile, ProA also played a role in autophagy induction in HCC cells. Defects in autophagy partially relieved ProA's anticancer effect in HCC cells. Our findings demonstrate that ProA can effectively inhibit HCC progression and may serve as a potential therapeutic agent for HCC treatment.