Brusatol, an NRF2 inhibitor for future cancer therapeutic
Brusatol, an NRF2 inhibitor for future cancer therapeutic
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DOI：
10.1186/s13578-019-0309-8
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发表时间：
2019-06-06
影响因子：
7.5
通讯作者：
Yang, Chunzhang
中科院分区：
文献类型：
--
作者：
Cai, Sabrina J.;Liu, Yang;Yang, Chunzhang
背景：长期以来，人们一直在研究草药天然产物作为癌症治疗药物的潜力。除了一些草药衍生的抗癌药物，如紫杉醇、长春新碱和鬼臼毒素的开发，许多最近的实验室研究结果表明，brusatol是一种从苏门答腊布鲁属种子中提取的准亚麻素，具有有效的肿瘤抑制作用，改善了疾病的预后。我们最近的发现进一步证明了brusatol与癌细胞内在代谢负担协同作用。本文综述了近年来brusatol作为实验性治疗人类恶性肿瘤（如白血病、肺癌、胰腺癌和脑肿瘤）的研究进展。我们还讨论了分子靶点brusatol，重点关注核因子红系2相关因子2 （NRF2）引导的基因转录，以及谷胱甘肽从头合成。此外，我们还讨论了brusatol在癌症治疗中的挑战和未来应用。结论：总之，我们相信越来越多的证据显示了brusatol作为一种新的癌症治疗策略的价值，这可能预示着未来的药物开发和临床转化。
Background: Natural products from herbal medicines have long been investigated for their potentials as cancer therapeutics. Besides the development of several herbal medicine-derived anti-cancer agents, such as paclitaxel, vincristine and podophyllotoxin, many recent laboratory findings demonstrated that brusatol, a quassinoid from the seeds of Brucea sumatrana, exhibits potent tumor suppressing effect with improved disease outcome. Our recent finding further demonstrated that brusatol synergizes with the intrinsic metabolic burden in cancer cells.Main body: Here, we summarized the recent investigations of brusatol as an experimental therapeutic for human malignancies, such as leukemia, lung cancer, pancreatic cancer and brain tumor. We also discussed the molecular target brusatol, with a focus on the Nuclear factor erythroid 2-related factor 2 (NRF2)-guided gene transcription, as well as glutathione de novo synthesis. Further, we discussed the challenges and future applications of brusatol for cancer therapy.Conclusion: In conclusion, we believe increasing evidences have shown the value of brusatol as a novel strategy for cancer treatment, which may indicate future drug development and clinical translation.