Taccalonolide A
(Synonyms: 根薯酮内酯A) 目录号 : GC37715
Taccalonolide A 是一种微管稳定剂，是从 Tacca chantrieri 中分离得到的类固醇，具有细胞毒性和抗疟活性。Taccalonolide A 能引起 G2-M 期滞留、Bcl-2 磷酸化，并引发细胞凋亡。Taccalonolide A 在体外对过表达 p 糖蛋白 (Pgp)、多药耐药蛋白 7 (MRP7) 的细胞系具有显著的抑制作用，抑制SK-OV-3细胞生长的 IC50 值为 622 nM。
Cas No.:108885-68-3
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
Taccalonolide A is a microtubule stabilizer, which is a steroid isolated from Tacca chantrieri, with cytotoxic and antimalarial activities[1][2]. Taccalonolide A causes G2-M accumulation, Bcl-2 phosphorylation and initiation of apoptosis[1]. Taccalonolide A is effective in vitro against cell lines that overexpress P-glycoprotein (Pgp) and multidrug resistance protein 7 (MRP7), with an IC50 of 622 nM for SK-OV-3 cells[3]. microtubule[1]
[1]. Tinley TL, et al. Taccalonolides E and A: Plant -derived steroids with microtubule-stabilizing activity. Cancer Res. 2003 Jun 15;63(12):3211-20. [2]. Risinger AL, et al. Taccalonolides: Novel microtubule stabilizers with clinical potential. Cancer Lett. 2010 May 1;291(1):14-9. [3]. Risinger AL, et al. The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms. Cancer Res. 2008 Nov 1;68(21):8881-8.
| Cas No. | 108885-68-3 | SDF | |
| 别名 | 根薯酮内酯A | ||
| Canonical SMILES | C[C@@]12[C@]([C@@H](OC(C)=O)[C@]3([H])[C@]2([H])[C@@H](C=C(O4)[C@@]3([C@](O)(C4=O)C)C)C)([H])[C@@]([C@H]5O)([H])[C@]([C@]6([C@H]([C@@H](O7)[C@@H]7C[C@]6([H])C5=O)OC(C)=O)C)([H])[C@H](OC(C)=O)[C@@H]1OC(C)=O | ||
| 分子式 | C36H46O14 | 分子量 | 702.74 |
| 溶解度 | Soluble in DMSO | 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 | 1.423 mL | 7.115 mL | 14.23 mL |
| 5 mM | 0.2846 mL | 1.423 mL | 2.846 mL |
| 10 mM | 0.1423 mL | 0.7115 mL | 1.423 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。
Anti-hepatoma effect of Taccalonolide A through suppression of sonic hedgehog pathway
Artif Cells Nanomed Biotechnol 2020 Dec;48(1):939-947.PMID:32496832DOI:10.1080/21691401.2020.1773484.
Taccalonolide A has been reported to have anti-tumour efficiency. However, the underlying mechanism for taccalonolides A therapy of hepatocellular carcinoma (HCC) is still obscure. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Apoptosis was determined by flow cytometry. Protein expression of B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax), sonic hedgehog (Shh), Smoothened (Smo) and Gli family zinc finger 1 (Gli1) was analyzed by western blot. The expression of Shh, Smo and Gli1 mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that Taccalonolide A inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G0/G1 phase, and improved the cytotoxicity of sorafenib in HCC cells. The expressions of Shh, Smo, Gli1 mRNA and protein were decreased after Taccalonolide A treatment. More importantly, activation of the Shh pathway attenuated taccalonolide A-induced inhibition on cell viability and promotion on apoptosis and cell cycle arrest in HCC. Also, activation of the Shh pathway neutralized the effect of Taccalonolide A on sorafenib cytotoxicity in HCC. We clarified that Taccalonolide A suppressed cell viability facilitated apoptosis, and improved the cytotoxicity of sorafenib in HCC by inhibition of the activation of the Shh pathway, providing alternative treatments for HCC.
Antitrypanosomal Activity of a Novel Taccalonolide from the Tubers of Tacca leontopetaloides
Phytochem Anal 2016 May;27(3-4):217-21.PMID:27313159DOI:10.1002/pca.2619.
Introduction: Several taccalonolides with various bioactivities have been isolated from Tacca species but no studies to isolate taccalonolides with anti-trypanosomal activity from Tacca leontopetaloides have been reported. Objectives: To analyse extracts of the roots of Tacca leontopetaloides, purify the extracts by column chromatography and identify isolated compounds by spectroscopic methods. The compounds and fractions will be tested for antitrypanosomal activity in vitro against Trypanosoma brucei brucei. Material and methods: Dried roots or tubers of Tacca leontopetaloides, chromatographic separation and spectroscopic identification. Results: A novel Taccalonolide A propanoate and some known taccalonolides were isolated and their structures were determined by NMR and mass spectrometry Conclusion: Several taccalonolides were isolated from Tacca leontopetaloides and were found to have in vitro antitrypanosomal activity against Trypanosoma brucei brucei and EC50 values for the isolated compounds were from 0.79 µg/mL. Copyright © 2016 John Wiley & Sons, Ltd.
Cellular studies reveal mechanistic differences between Taccalonolide A and paclitaxel
Cell Cycle 2011 Jul 1;10(13):2162-71.PMID:21597323DOI:10.4161/cc.10.13.16238.
Taccalonolide A is a microtubule stabilizer that has cellular effects almost identical to paclitaxel. However, biochemical studies show that, unlike paclitaxel, Taccalonolide A does not enhance purified tubulin polymerization or bind tubulin/microtubules. Mechanistic studies aimed at understanding the nature of the differences between Taccalonolide A and paclitaxel were conducted. Our results show that Taccalonolide A causes bundling of interphase microtubules at concentrations that cause antiproliferative effects. In contrast, the concentration of paclitaxel that initiates microtubule bundling is 31-fold higher than its IC 50. Taccalonolide A's effects are further differentiated from paclitaxel in that it is unable to enhance the polymerization of tubulin in cellular extracts. This finding extends previous biochemical results with purified brain tubulin to demonstrate that Taccalonolide A requires more than tubulin and a full complement of cytosolic proteins to cause microtubule stabilization. Reversibility studies were conducted and show that the cellular effects of Taccalonolide A persist after drug washout. In contrast, other microtubule stabilizers, including paclitaxel and laulimalide, demonstrate a much higher degree of cellular reversibility in both short-term proliferation and long-term clonogenic assays. The propensity of Taccalonolide A to alter interphase microtubules at antiproliferative concentrations as well as its high degree of cellular persistence may explain why Taccalonolide A is more potent in vivo than would be expected from cellular studies. The close linkage between the microtubule bundling and antiproliferative effects of Taccalonolide A is of interest given the recent hypothesis that the effects of microtubule targeting agents on interphase microtubules might play a prominent role in their clinical anticancer efficacy.
Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity
Cancer Res 2003 Jun 15;63(12):3211-20.PMID:12810650doi
During the course of a mechanism-based screening program designed to identify new microtubule-disrupting agents from natural products, we identified a crude extract from Tacca chantrieri that initiated Taxol-like microtubule bundling. Bioassay-directed purification of the extract yielded the highly oxygenated steroids taccalonolides E and A. The taccalonolides caused an increased density of cellular microtubules in interphase cells and the formation of thick bundles of microtubules similar to the effects of Taxol. Mitotic cells exhibited abnormal mitotic spindles containing three or more spindle poles. The taccalonolides were evaluated for antiproliferative effects in drug-sensitive and multidrug-resistant cell lines. The data indicate that taccalonolide E is slightly more potent than Taccalonolide A in drug-sensitive cell lines and that both taccalonolides are effective inhibitors of cell proliferation. Both taccalonolides are poorer substrates for transport by P-glycoprotein than Taxol. The ability of the taccalonolides to circumvent mutations in the Taxol-binding region of beta-tubulin was examined using the PTX 10, PTX 22, and 1A9/A8 cell lines. The data suggest little cross-resistance of Taccalonolide A as compared with Taxol, however, the data from the PTX 22 cell line indicate a 12-fold resistance to taccalonolide E, suggesting a potential overlap of binding sites. Characteristic of agents that disrupt microtubules, the taccalonolides caused G(2)-M accumulation, Bcl-2 phosphorylation, and initiation of apoptosis. The taccalonolides represent a novel class of plant-derived microtubule-stabilizers that differ structurally and biologically from other classes of microtubule-stabilizers.
Hydrolysis reactions of the taccalonolides reveal structure-activity relationships
J Nat Prod 2013 Jul 26;76(7):1369-75.PMID:23855953DOI:10.1021/np400435t.
The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca that show potent in vivo antitumor activity and the ability to overcome multiple mechanisms of drug resistance. The most potent taccalonolide identified to date, AJ, is a semisynthetic product generated from the major plant metabolite Taccalonolide A in a two-step reaction. The first step involves hydrolysis of Taccalonolide A to generate taccalonolide B, and then this product is oxidized to generate an epoxide group at C-22-C-23. To generate sufficient taccalonolide AJ for in vivo antitumor efficacy studies, the hydrolysis conditions for the conversion of Taccalonolide A to B were optimized. During purification of the hydrolysis products, we identified the new taccalonolide AO (1) along with taccalonolide I. When the same hydrolysis reaction was performed on a taccalonolide E-enriched fraction, four new taccalonolides, assigned as AK, AL, AM, and AN (2-5), were obtained in addition to the expected product taccalonolide N. Biological assays were performed on each of the purified taccalonolides, which allowed for increased refinement of the structure-activity relationship of this class of compounds.