Brusatol: A potential anti-tumor quassinoid from Brucea javanica

Yu, Xiao‐Qi; Shang, Xiuli; Huang, Xiao‐Xiao; Yao, Guo‐Dong; Song, Shao‐Jiang

doi:10.1016/j.chmed.2020.05.007

Cited by 23 publications

(10 citation statements)

References 60 publications

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“…Furthermore, cooperative effects of brusatol and other anticancer agents, including gemcitabine (in pancreatic carcinomas) [ 84 ], cytarabine (Ara-C) (in acute myeloid leukemia) [ 85 ], luteolin (in gastric cancers) [ 86 ], and paclitaxel (in BCs) [ 87 , 88 ], were observed. Other studies supported clinical applications of Nrf2 inhibition by brusatol in different cancers [ 30 , 35 , 89 ]. The disruption of Nrf2 nuclear export prevented the nuclear accumulation of this protein and sensitized A549 cells to cisplatin and carboplatin [ 80 ].…”

Section: Discussionmentioning

confidence: 80%

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

et al. 2021

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Nuclear factor erythroid-2 related factor-2 (Nrf2) is an oxidative stress-response transcriptional activator that promotes carcinogenesis through metabolic reprogramming, tumor promoting inflammation, and therapeutic resistance. However, the extension of Nrf2 expression and its involvement in regulation of breast cancer (BC) responses to chemotherapy remain largely unclear. This study determined the expression of Nrf2 in BC tissues (n = 46) and cell lines (MDA-MB-453, MCF-7, MDA-MB-231, MDA-MB-468) with diverse phenotypes. Immunohistochemical (IHC)analysis indicated lower Nrf2 expression in normal breast tissues, compared to BC samples, although the difference was not found to be significant. However, pharmacological inhibition and siRNA-induced downregulation of Nrf2 were marked by decreased activity of NADPH quinone oxidoreductase 1 (NQO1), a direct target of Nrf2. Silenced or inhibited Nrf2 signaling resulted in reduced BC proliferation and migration, cell cycle arrest, activation of apoptosis, and sensitization of BC cells to cisplatin in vitro. Ehrlich Ascites Carcinoma (EAC) cells demonstrated elevated levels of Nrf2 and were further tested in experimental mouse models in vivo. Intraperitoneal administration of pharmacological Nrf2 inhibitor brusatol slowed tumor cell growth . Brusatol increased lymphocyte trafficking towards engrafted tumor tissue in vivo, suggesting activation of anti-cancer effects in tumor microenvironment. Further large-scale BC testing is needed to confirm Nrf2 marker and therapeutic capacities for chemo sensitization in drug resistant and advanced tumors.

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Section: Discussionmentioning

confidence: 80%

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

et al. 2021

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“…In addition, BD has been found to inhibit hepatocellular carcinoma by inhibiting signaling pathways related to liver carcinogenesis and disease progression [ 35 ]. Quassinoids are typically more potent than fatty acids, with 50% inhibitory concentration (IC 50 ) values down to the nanomolar level [ 37 ], and hence most therapeutic focus has been on quassinoids [ 38 , 39 ].…”

Section: Overview Of Brucea Javanica Oil and Momentioning

confidence: 99%

Medicinal Activities and Nanomedicine Delivery Strategies for Brucea javanica Oil and Its Molecular Components

et al. 2020

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Brucea javanica oil (BJO) is widely used in traditional Chinese medicine to treat various types of cancer and inflammatory diseases. There is significant interest in understanding the medicinal activities of BJO and its molecular components, especially quassinoids, and in exploring how they can be incorporated into nanomedicine delivery strategies for improved application prospects. Herein, we cover the latest progress in developing different classes of drug delivery vehicles, including nanoemulsions, liposomes, nanostructured lipid carriers, and spongosomes, to encapsulate BJO and purified quassinoids. An introduction to the composition and medicinal activities of BJO and its molecular components, including quassinoids and fatty acids, is first provided. Application examples involving each type of drug delivery vehicle are then critically presented. Future opportunities for nanomedicine delivery strategies in the field are also discussed and considered within the context of translational medicine needs and drug development processes.

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“…Several other reports have demonstrated the effective Nrf2 inhibitory role of BT in the management of pancreatic and colorectal cancers [119,120]. A recent review also reported BT to be a specific Nrf2 inhibitor and described its anticancer role in the amelioration of various cancers [121]. However, a recent report demonstrated the role of enhanced Nrf2/HO-1 signaling in mediating the tumor suppressing effect of BT in U-251 glioma cells [122].…”

Section: Brusatol (Bt)mentioning

confidence: 99%

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

et al. 2021

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ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.

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Brusatol: A potential anti-tumor quassinoid from Brucea javanica

Cited by 23 publications

References 60 publications

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

Medicinal Activities and Nanomedicine Delivery Strategies for Brucea javanica Oil and Its Molecular Components

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

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