Brusatol鸦胆子苦醇AbMoleM8710是一种从植物鸦胆子Brucea javanica中分离得到的喹啉类天然化合物能抑制细胞蛋白的从头合成并在多种细胞和动物模型中展现出显著的生物学活性。在细胞实验中BrusatolCAS No.14907-98-3以剂量和时间依赖性方式抑制多种癌细胞系的增殖包括非小细胞肺癌细胞A549、H1650、PC9和HCC827[1]鼻咽癌细胞CNE-1、CNE-2、5-8F和6-10B[2]急性淋巴细胞白血病ALL细胞系KOPN-8B-ALL、CEM和MOLT-4T-ALL[3]胶质瘤细胞LN229和U251[4]。Brusatol鸦胆子苦醇作用机制涉及多个通路首先Brusatol鸦胆子苦醇AbMoleM8710可抑制核因子E2相关因子2Nrf2通路从而削弱细胞的抗氧化能力导致活性氧ROS显著积累[5]BrusatolCAS No.14907-98-3还能诱导线粒体膜电位下降激活Caspase-3/7/9及PARP切割促进线粒体依赖性凋亡[6]引起G0/G1或G2/M期细胞周期阻滞伴随Cyclin B1、Cdc25c、Cdc2 p34和Cyclin D1等调控蛋白表达改变[3]抑制PI3K/Akt/mTOR信号通路表现为p-PI3K和p-AKT水平降低并上调PTEN表达同时Brusatol鸦胆子苦醇还能抑制上皮-间质转化EMT上调E-cadherin下调N-cadherin和vimentin此外Brusatol还能促进铁死亡Ferroptosis并下调PLK1、SCD1及KLF4/NCK2轴等关键分子。在动物实验中Brusatol鸦胆子苦醇NSC 172924AbMoleM8710在C57BL/6小鼠高脂饮食模型中以2周疗程改善葡萄糖耐量和胰岛β细胞功能[7]在裸鼠异种移植模型中腹腔或尾静脉给药可显著抑制Cal-27舌鳞癌[8]、CNE-1鼻咽癌、Hucc-T1ICC、Bel7404肝癌及胶质瘤等肿瘤生长常用剂量范围为1–5 mg/kg如1 mg/kg隔日一次或2 mg/kg每日一次在斑马鱼幼虫模型中BrusatolBrusatol鸦胆子苦醇的LC50为0.010 ± 0.122 ppmLC90为0.654 ± 0.081 ppm且高浓度下引起明显形态学损伤[9]药代动力学研究显示经尾静脉单次给药后Brusatol在小鼠血浆中迅速清除但在组织中分布广泛尤其在部分组织中的浓度可比血浆高10倍以上[10]。综上Brusatol鸦胆子苦醇NSC 172924AbMoleM8710通过多通路、多靶点机制在多种细胞系和啮齿类动物模型中表现出强效的抗增殖、促凋亡、抗迁移及调控细胞命运的作用是当前肿瘤生物学研究中的重要工具化合物。参考文献及鸣谢[1] Xie, J.; Lai, Z.; Zheng, X.; et al. Apoptotic activities of brusatol in human non-small cell lung cancer cells: Involvement of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response. Toxicology2021, 451, 152680.[2] Guo, S.; Zhang, J.; Wei, C.; et al. Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway. Cancer chemotherapy and pharmacology2020, 85 (6), 1097-1108.[3] Jorge, J.; Magalhaes, N.; Alves, R.; et al. Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation. Biomedicines2022, 10 (9).[4] Chen, Z.; He, B.; Zhao, J.; et al. Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology2022, 104, 154323.[5] Guo, N.; Zhang, Y.; Yuan, G.; et al. Pharmacokinetics and nephrotoxicity of cisplatin modulated by combination therapy with brusatol. Frontiers in pharmacology2026, 17, 1708101.[6] Huang, C. H.; Wang, F. T.; Chan, W. H. Role of caspase-3-cleaved/activated PAK2 in brusatol-triggered apoptosis of human lung cancer A549 cells. Toxicology research2022, 11 (5), 791-803.[7] Turpaev, K.; Krizhanovskii, C.; Wang, X.; et al. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB journal : official publication of the Federation of American Societies for Experimental Biology2019, 33 (3), 3510-3522.[8] Qi, S.; Li, D.; Deng, F.; et al. Brusatol modulates the Nrf2/GCLC pathway to enhance ferroptosis in the treatment of oral squamous cell carcinoma. European journal of pharmacology2025, 1003, 177935.[9] Sutiningsih, D.; Nurjazuli, N.; Nugroho, D.; et al. Larvicidal Activity of Brusatol Isolated from Brucea javanica (L) Merr on Culex quinquefasciatus. Iranian journal of public health2019, 48 (4), 688-696.[10] Guo, N.; Zhang, X.; Bu, F.; et al. Determination of brusatol in plasma and tissues by LC-MS method and its application to a pharmacokinetic and distribution study in mice. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences2017, 1053, 20-26.细胞实验参考细胞系MDA-MB-468 cells方法HCECs were pretreated with 15 nM brusatol (Nrf2 inhibitor, Abmole, USA) or 10 µM ZnPP for 1 h prior to TQ treatment. Subsequently, the cells were stimulated with C. albicans conidia for 8 h (PCR) or 24 h浓度15 nM处理时间1 h参考文献Cytokine. 2023 Dec;172:156375.* 上述方法来自公开文献仅供相同目的实验参考。如实验目的、材料、方法不同请参考其他文献。
AbMole丨Brusatol鸦胆子苦醇：多靶点抗肿瘤天然化合物的科研应用
发布时间：2026/5/21 0:45:34
Brusatol鸦胆子苦醇AbMoleM8710是一种从植物鸦胆子Brucea javanica中分离得到的喹啉类天然化合物能抑制细胞蛋白的从头合成并在多种细胞和动物模型中展现出显著的生物学活性。在细胞实验中BrusatolCAS No.14907-98-3以剂量和时间依赖性方式抑制多种癌细胞系的增殖包括非小细胞肺癌细胞A549、H1650、PC9和HCC827[1]鼻咽癌细胞CNE-1、CNE-2、5-8F和6-10B[2]急性淋巴细胞白血病ALL细胞系KOPN-8B-ALL、CEM和MOLT-4T-ALL[3]胶质瘤细胞LN229和U251[4]。Brusatol鸦胆子苦醇作用机制涉及多个通路首先Brusatol鸦胆子苦醇AbMoleM8710可抑制核因子E2相关因子2Nrf2通路从而削弱细胞的抗氧化能力导致活性氧ROS显著积累[5]BrusatolCAS No.14907-98-3还能诱导线粒体膜电位下降激活Caspase-3/7/9及PARP切割促进线粒体依赖性凋亡[6]引起G0/G1或G2/M期细胞周期阻滞伴随Cyclin B1、Cdc25c、Cdc2 p34和Cyclin D1等调控蛋白表达改变[3]抑制PI3K/Akt/mTOR信号通路表现为p-PI3K和p-AKT水平降低并上调PTEN表达同时Brusatol鸦胆子苦醇还能抑制上皮-间质转化EMT上调E-cadherin下调N-cadherin和vimentin此外Brusatol还能促进铁死亡Ferroptosis并下调PLK1、SCD1及KLF4/NCK2轴等关键分子。在动物实验中Brusatol鸦胆子苦醇NSC 172924AbMoleM8710在C57BL/6小鼠高脂饮食模型中以2周疗程改善葡萄糖耐量和胰岛β细胞功能[7]在裸鼠异种移植模型中腹腔或尾静脉给药可显著抑制Cal-27舌鳞癌[8]、CNE-1鼻咽癌、Hucc-T1ICC、Bel7404肝癌及胶质瘤等肿瘤生长常用剂量范围为1–5 mg/kg如1 mg/kg隔日一次或2 mg/kg每日一次在斑马鱼幼虫模型中BrusatolBrusatol鸦胆子苦醇的LC50为0.010 ± 0.122 ppmLC90为0.654 ± 0.081 ppm且高浓度下引起明显形态学损伤[9]药代动力学研究显示经尾静脉单次给药后Brusatol在小鼠血浆中迅速清除但在组织中分布广泛尤其在部分组织中的浓度可比血浆高10倍以上[10]。综上Brusatol鸦胆子苦醇NSC 172924AbMoleM8710通过多通路、多靶点机制在多种细胞系和啮齿类动物模型中表现出强效的抗增殖、促凋亡、抗迁移及调控细胞命运的作用是当前肿瘤生物学研究中的重要工具化合物。参考文献及鸣谢[1] Xie, J.; Lai, Z.; Zheng, X.; et al. Apoptotic activities of brusatol in human non-small cell lung cancer cells: Involvement of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response. Toxicology2021, 451, 152680.[2] Guo, S.; Zhang, J.; Wei, C.; et al. Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway. Cancer chemotherapy and pharmacology2020, 85 (6), 1097-1108.[3] Jorge, J.; Magalhaes, N.; Alves, R.; et al. Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation. Biomedicines2022, 10 (9).[4] Chen, Z.; He, B.; Zhao, J.; et al. Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology2022, 104, 154323.[5] Guo, N.; Zhang, Y.; Yuan, G.; et al. Pharmacokinetics and nephrotoxicity of cisplatin modulated by combination therapy with brusatol. Frontiers in pharmacology2026, 17, 1708101.[6] Huang, C. H.; Wang, F. T.; Chan, W. H. Role of caspase-3-cleaved/activated PAK2 in brusatol-triggered apoptosis of human lung cancer A549 cells. Toxicology research2022, 11 (5), 791-803.[7] Turpaev, K.; Krizhanovskii, C.; Wang, X.; et al. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB journal : official publication of the Federation of American Societies for Experimental Biology2019, 33 (3), 3510-3522.[8] Qi, S.; Li, D.; Deng, F.; et al. Brusatol modulates the Nrf2/GCLC pathway to enhance ferroptosis in the treatment of oral squamous cell carcinoma. European journal of pharmacology2025, 1003, 177935.[9] Sutiningsih, D.; Nurjazuli, N.; Nugroho, D.; et al. Larvicidal Activity of Brusatol Isolated from Brucea javanica (L) Merr on Culex quinquefasciatus. Iranian journal of public health2019, 48 (4), 688-696.[10] Guo, N.; Zhang, X.; Bu, F.; et al. Determination of brusatol in plasma and tissues by LC-MS method and its application to a pharmacokinetic and distribution study in mice. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences2017, 1053, 20-26.细胞实验参考细胞系MDA-MB-468 cells方法HCECs were pretreated with 15 nM brusatol (Nrf2 inhibitor, Abmole, USA) or 10 µM ZnPP for 1 h prior to TQ treatment. Subsequently, the cells were stimulated with C. albicans conidia for 8 h (PCR) or 24 h浓度15 nM处理时间1 h参考文献Cytokine. 2023 Dec;172:156375.* 上述方法来自公开文献仅供相同目的实验参考。如实验目的、材料、方法不同请参考其他文献。
