Gambogenic acid
(Synonyms: 新藤黄酸) 目录号 : GC38062
Gambogenic Acid, identified from Gamboge, is an inhibitor of the FGFR signaling pathway in erlotinib-resistant non-small-cell lung cancer (NSCLC) and exhibits anti-tumor effects. Gambogenic acid acts is also an effective inhibitor of EZH2 that specifically and covalently binds to Cys668 within the EZH2-SET domain, and triggers EZH2 ubiquitination.
Cas No.:173932-75-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Gambogenic Acid, identified from Gamboge, is an inhibitor of the FGFR signaling pathway in erlotinib-resistant non-small-cell lung cancer (NSCLC) and exhibits anti-tumor effects. Gambogenic acid acts is also an effective inhibitor of EZH2 that specifically and covalently binds to Cys668 within the EZH2-SET domain, and triggers EZH2 ubiquitination.
Gambogenic acid as a novel agent that specifically and covalently bound to Cys668 within the EZH2‐SET domain, triggers EZH2 degradation through COOH terminus of Hsp70‐interacting protein (CHIP)‐mediated ubiquitination. Gambogenic acid significantly suppresses H3K27Me3 and effectively reactivated polycomb repressor complex 2 (PRC2)‐silenced tumor suppressor genes. Gambogenic acid significantly suppresses tumor growth in an EZH2‐dependent manner.[1]
In xenograft mouse model, gambogenic acid derivative GNA002 significantly decreases the volumes of Cal‐27‐derived tumors, and reduces H3K27Me3 levels in tumor tissues.
[1] Xu Wang, et al. EMBO J . 2017 May 2;36(9):1243-1260. [2] Linfeng Xu, et al. Cell Death Dis . 2018 Feb 15;9(3):262.
| Cas No. | 173932-75-7 | SDF | |
| 别名 | 新藤黄酸 | ||
| Canonical SMILES | O=C(O)/C(C)=C\C[C@@]1(C2=O)OC(C)(C)[C@]([C@]31OC4=C5C(O)=C(C/C=C(C)/CC/C=C(C)\C)C(O)=C4C/C=C(C)\C)([H])C[C@@]2([H])C=C3C5=O | ||
| 分子式 | C38H46O8 | 分子量 | 630.77 |
| 溶解度 | DMSO: 250 mg/mL (396.34 mM) | 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 | 1.5854 mL | 7.9268 mL | 15.8536 mL |
| 5 mM | 0.3171 mL | 1.5854 mL | 3.1707 mL |
| 10 mM | 0.1585 mL | 0.7927 mL | 1.5854 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。
Gambogenic acid Inhibits Basal Autophagy of Drug-Resistant Hepatoma Cells and Improves Its Sensitivity to Adriamycin
Biol Pharm Bull 2022;45(1):63-70.PMID:34980780DOI:10.1248/bpb.b21-00511.
Gambogenic acid (GNA) is extracted from plant Gamboge, has a wide range of anti-tumor effects. In this paper, we study the inhibitory effect of GNA on the BEL-7402/ADM of hepatoma resistant cell lines and further study the mechanism of action. Cell viability test represented that GNA could improve the sensitivity of hepatoma drug-resistant cell line BEL-7402/ADM to Adriamycin (ADM), and further study by 4',6-diamidino-2-phenylindole (DAPI) staining and flow cytometry found that GNA could improve the effect of ADM on promoting apoptosis in BEL-7402/ADM cells, and the activation of apoptosis-related protein was significantly increased, and the ratio of Bax to Bcl-2 was significantly increased. Monodansylcadaverine staining and transmission electron microscopy showed that the basal autophagy level of BEL-7402/ADM cells was higher than that of BEL-7402 cells. Further detection of protein expression found that the intracellular LC3-II to LC3-I ratio and Beclin 1 protein expression increased in the combination of GNA and ADM, but the protein level of p62 increased significantly. GNA inhibit protective autophagy in BEL-7402/ADM cells and promote the role of ADM in inducing apoptosis, thereby increasing ADM sensitivity to BEL-7402/ADM cells, and the effect of GNA inhibition of autophagy may be achieved by inhibiting the degradation of autophagosomes.
Gambogenic acid antagonizes the expression and effects of long non-coding RNA NEAT1 and triggers autophagy and ferroptosis in melanoma
Biomed Pharmacother 2022 Oct;154:113636.PMID:36081284DOI:10.1016/j.biopha.2022.113636.
In this study, we investigated the molecular mechanism underlying melanoma proliferation, with the aim to discover effective interventions which may markedly improve clinical prognosis. The results showed that Gambogenic acid (GNA) could inhibit the proliferation of melanoma cells in vivo (C57BL/6 mice) and in vitro. Long non-coding RNA sequencing was used to identify the most significant long non-coding RNA, i.e., nuclear enriched abundant transcript 1 (NEAT1). NEAT1 was is up-regulated in melanoma, which was found to closely relate to cell proliferation. Melanoma cell lines either over-expressing NEAT1 or with NEAT1 knockdown was established through cloning experiments. A model of transplanted tumors was established to verify the inhibitory effect of GNA on the proliferation of melanoma cells in vitro and in vivo by downregulating NEAT1. Downregulation of NEAT1-induced ferroptosis and autophagy was demonstrated by detecting the effects of NEAT1 overexpressed and downregulated melanoma cell lines and melanoma transplantation model mice. Mechanistically, downregulation of NEAT1 can weaken the direct binding of Slc7a11, indirectly leading to inhibiting GPX-4 activity and subsequent ferroptosis, while, mediating the AMPK/mTOR signal axis-induced autophagy. The levels of Furthermore, NEAT1 decrease under the treatment of Gambogenic acid (GNA), a promising natural anticancer compound, while NEAT1 overexpression suppresses GNA inhibition on cell vitality and eliminates GNA-induced melanoma cell ferroptosis and autophagy.
Gambogenic acid alleviates kidney fibrosis via epigenetic inhibition of EZH2 to regulate Smad7-dependent mechanism
Phytomedicine 2022 Nov;106:154390.PMID:35994849DOI:10.1016/j.phymed.2022.154390.
Background: Epigenetics regulating gene expression plays important role in kidney fibrosis. Natural products originating from diverse sources including plants and microorganisms are capable to influence epigenetic modifications. Gambogenic acid (GNA) is a caged xanthone extracted from gamboge resin, exudation of Garcinia hanburyi Hook.f., and the effect of GNA on kidney fibrosis with its underlying mechanism on epigenetics remains unknown. Purpose: This study aimed to explore the role of GNA against kidney fibrogenesis by histone methylation mediating gene expression. Methods: Two experimental mice of unilateral ureteral obstruction (UUO) and folic acid (FA) were given two dosages of GNA (3 and 6 mg/kg/d). TGF-β1 was used to stimulate mouse tubular epithelial (TCMK-1) cells and siRNAs were transfected to verify the underlying mechanisms of GNA. Histological changes were evaluated by HE, MASSON stainings, immunohistochemistry and immunofluorescence. Western blot and qPCR were used to measure protein/gene transcription levels. Results: GNA dose-dependently alleviated UUO-induced kidney fibrosis and FA-induced kidney early fibrosis, indicated by the pathology and fibrotic factor changes (α-SMA, collagen I, collagen VI, and fibronectin). Mechanically, GNA reduced enhancer of zeste homolog 2 (EZH2) and H3K27me3, promoted Smad7 transcription, and inhibited TGF-β/Smad3 fibrotic signaling in injured kidneys. Moreover, with TGF-β1-induced EZH2 increasing, GNA suppressed α-SMA, fibronectin and collagen levels in tubular epithelial TCMK-1 cells. Although partially decreasing EZH2, GNA did not influence fibrotic signaling in Smad7 siRNA-transfected TCMK-1 cells. Conclusion: Epigenetic inhibition of EZH2 by GNA ameliorated kidney fibrogenesis via regulating Smad7-meidated TGF-β/Smad3 signaling.
Gambogenic acid induction of apoptosis in a breast cancer cell line
Asian Pac J Cancer Prev 2013;14(12):7601-5.PMID:24460340DOI:10.7314/apjcp.2013.14.12.7601.
Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including an A549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mouse models to detect the effect of Gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members. Results: We found that Gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.
Gambogenic acid induced mitochondrial-dependent apoptosis and referred to phospho-Erk1/2 and phospho-p38 MAPK in human hepatoma HepG2 cells
Environ Toxicol Pharmacol 2012 Mar;33(2):181-90.PMID:22222560DOI:10.1016/j.etap.2011.12.006.
Gambogenic acid, identified from Gamboge, is responsible for anti-tumor effects, and has been shown to be a potential molecule against human cancers. In this study, the molecular mechanism of gambogenic acid-induced apoptosis in HepG2 cells was investigated. Gambogenic acid significantly inhibited cell proliferation and induced apoptosis. Acridine orange/ethidium bromide (AO/EB) staining was used to observe apoptosis, and then confirmed by transmission electron microscopy. Gambogenic acid induced apoptosis and morphological changes in mitochondria, and intracellular reactive oxygen species (ROS) and mitochondrial membrane permeabilization (MMP) in mitochondrial apoptosis pathway were also examined. Results showed that the levels of phospho-p38 and its downstream phospho-Erk1/2 of HepG2 cells increased in time- and concentration-dependent manners after Gambogenic acid treatments. Additionally, Gambogenic acid increased expression ratio of Bcl-2/Bax in mRNA levels, Western blotting analysis also further confirmed the reduced level of Bcl-2 and increase the expression level of Bax in HepG2 cells. These results indicated that Gambogenic acid induced mitochondrial oxidative stress and activated caspases through a caspase-3 and caspase-9-dependent apoptosis pathway. Moreover, Gambogenic acid mediated apoptosis and was involved in the phospho-Erk1/2 and phospho-p38 MAPK proteins expression changes in HepG2 cells.