Brusatol
(Synonyms: 鸦胆子苦醇; NSC 172924) 目录号 : GC34070
Brusatol是一种Nrf2抑制剂，由从鸦嘴茅中分离提取。
Cas No.:14907-98-3
Sample solution is provided at 25 µL, 10mM.
Brusatol is an Nrf2 inhibitor isolated from Brucea javanica and exhibits significant tumor inhibition in multiple cancers through decreased resistance to cancer oxidative stress injury[1,2,3]. Brusatol is confirmed to inhibit the Nrf2-Notch1 pathway, increse p-P38, LC3, Beclin 1 and p-JNK expression, downregulate BRF2, IGFBP-2, P62 and CD151[3].
In vitro, Brusatol (20, 50, 100, and 200nM; 0, 24, 48, 72, and 96h) treatment at the zygotic stage prevented the early embryo development in Kunming mice embryos[4]. Brusatol (1 and 100nM; 72h) shows an antitumor effect in an acute lymphoblastic leukemia (KOPN-8 cells) model triggered by reactive oxygen species accumulation[5]. Brusatol (0.31 to 10µM; 24 or 48h) results in breast cancer retardation via Nrf2 inhibition in breast cancer cell lines[6].
In vivo, Brusatol (2mg/kg; every 48h; 5 weeks; i.p.) hinders the progression of bladder cancer by Chac1/Nrf2/SLC7A11 pathway[7]. Brusatol (NSC 172924) sensitizes endometrial hyperplasia and cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism in a Brusatol (NSC 172924)-treated (10nmol/l; 3 days) endometrial cancer cell (Ishikawa and ECC1) injected nude mice model[8].
References:
[1] Yu, Xiao-Qi et al. “Brusatol: A potential anti-tumor quassinoid from *Brucea javanica*.” *Chinese herbal medicines* vol. 12,4 359-366. 19 Aug. 2020, doi:10.1016/j.chmed.2020.05.007
[2] Sutiningsih, Dwi et al. “Larvicidal Activity of Brusatol Isolated from *Brucea javanica* (L) Merr on *Culex quinquefasciatus*.” *Iranian journal of public health* vol. 48,4 (2019): 688-696.
[3] Li, Kun-Wei et al. “Brucea javanica: A review on anticancer of its pharmacological properties and clinical researches.” *Phytomedicine : international journal of phytotherapy and phytopharmacology* vol. 86 (2021): 153560. doi:10.1016/j.phymed.2021.153560
[4] Lin, Ying et al. “Nrf2 inhibition affects cell cycle progression during early mouse embryo development.” *The Journal of reproduction and development*vol. 64,1 (2018): 49-55. doi:10.1262/jrd.2017-042
[5] Jorge, Joana et al. “Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation.” *Biomedicines* vol. 10,9 2207. 6 Sep. 2022, doi:10.3390/biomedicines10092207
[6] Bovilla, Venugopal R et al. “Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo.” *Biomedicines* vol. 9,9 1119. 30 Aug. 2021, doi:10.3390/biomedicines9091119
[7] Yu, Xi et al. “Brusatol hinders the progression of bladder cancer by Chac1/Nrf2/SLC7A11 pathway.” *Experimental cell research* vol. 438,2 (2024): 114053. doi:10.1016/j.yexcr.2024.114053
[8] Hu, Meiyan et al. “Brusatol sensitizes endometrial hyperplasia and cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism.” *Laboratory investigation; a journal of technical methods and pathology* vol. 102,12 (2022): 1335-1345. doi:10.1038/s41374-022-00816-5
Brusatol是一种Nrf2抑制剂，由从鸦嘴茅中分离提取[1]。Brusatol通过降低对癌症氧化应激损伤的抵抗，在多种癌症模型中表现出显著的肿瘤抑制作用[2,3]。Brusatol被证实抑制Nrf2-Notch1通路，增加p-P38、LC3、Beclin 1和p-JNK的表达，下调BRF2、IGFBP-2、P62和CD151的作用[3]。
在体外，Brusatol(20、50、100和200nM；0、24、48、72和96h)可阻止昆明小鼠在合子期胚胎的早期胚胎发育[4]。Brusatol(1, 100nM；72h)在活性氧积累触发的急性淋巴细胞白血病模型（KOPN-8细胞）中显示出抗肿瘤作用[5]。Brusatol(0.31 ~ 10µM；24h或48h)通过Nrf2抑制乳腺癌细胞系导致乳腺癌发育迟缓[6]。
在体内，Brusatol (2mg/kg；每48小时一次，持续5周；腹腔注射)通过Chac1/Nrf2/SLC7A11通路阻碍膀胱癌的进展[7]。Brusatol处理的子宫内膜癌细胞（Ishikawa和ECC1）注射的裸鼠肿瘤模型中中，Brusatol通过抑制NRF2-TET1-AKR1C1介导的黄体酮代谢，使子宫内膜增生和癌症对黄体酮产生敏感[8]。
| Cell experiment [1]: | |
Cell lines | MCF-7, MDA-MB-231, or MDA-MB-468 |
Preparation Method | Various BC cells (MCF-7, MDA-MB-231, or MDA-MB-468) (1.0 × 104cells in 100µL DMEM with 10% FBS) were seeded in 96-well plates and cultured in an incubator at 37 °C with 5% CO2 and 90% relative humidity. Following this, when cell confluence reached about 60 to 70% (36h later), the cells were exposed to gradual concentrations of brusatol (ranging from 0.31 to 10µM) for 24 or 48h. Following this treatment, cell viability was measured using sulforhodamine B (SRB) and MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays. |
Reaction Conditions | 0.31 to 10µM; 24 or 48h |
Applications | The effect of two low/non-toxic concentrations (19.5 and 78nM) of brusatol did not demonstrate any significant effect on cell viability. Brusatol provoked a significant decrease in BC cell viability; however, this effect was not dose- or time-dependent. The highest cytotoxic effects of brusatol were observed at 24 and 48h of treatment. |
| Animal experiment [2]: | |
Animal models | male BALB/c-nude mice |
Preparation Method | T24 cells were injected subcutaneously into mice at a concentration of 1×106 cells per mouse. Three mice were randomly allocated into two groups, consisting of nude mice. The experimental groups were administered intraperitoneal injections of brusatol at a dosage of 2mg/kg every 48h, whereas the control groups were given injections of normal saline. Following a treatment duration of 5 weeks, the mice were administered anesthesia and subsequently euthanized to facilitate additional analysis. Sodium pentobarbital (30mg/kg) was administered as the anesthetic drug. |
Dosage form | 2mg/kg; every 48h; 5 weeks |
Applications | The tumor size of mice treated with brusatol was significantly reduced. |
References: | |
| Cas No. | 14907-98-3 | SDF | |
| 别名 | 鸦胆子苦醇; NSC 172924 | ||
| Canonical SMILES | CC([C@](C[C@@](O1)2[H])3[H])=C(O)C(C[C@]3(C)[C@]4([H])[C@]2(CO[C@@]5([C@@H](O)[C@@H]4O)C(OC)=O)[C@@]5([H])[C@@H](OC(/C=C(C)/C)=O)C1=O)=O | ||
| 分子式 | C26H32O11 | 分子量 | 520.53 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml | 储存条件 | 4°C, protect from light, stored under nitrogen |
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9211 mL | 9.6056 mL | 19.2112 mL |
| 5 mM | 0.3842 mL | 1.9211 mL | 3.8422 mL |
| 10 mM | 0.1921 mL | 0.9606 mL | 1.9211 mL |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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