Brusatol inhibits the invasion and migration of pancreatic cancer cells by suppressing the NRF2/NF-κB/STAT3 signal cascade

Xiang, Yukai; Dai, Shengjie; Li, Ding; Zhu, Xiandong; Su, Jiadong; Chen, Bicheng; Wu, Minmin

doi:10.1016/j.jff.2022.105024

Cited by 2 publications

(3 citation statements)

References 31 publications

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“…Terpenoid molecules have been proposed as effective NRF2 inhibitors and potential chemotherapeutics. This was recently confirmed by Xiang et al for brusatol [ 137 ], a triterpenoid lactone, which proved to be an effective inhibitor of cell invasion and migration via NRF2 pathway. For another bioactive diterpenoid, oridonine, the inhibitory effect of its terpenoid moiety on the NRF2 pathway was confirmed in human osteosarcoma cells, associated with the promotion of apoptotic effect, in vitro and in vivo [ 138 ].…”

Section: Plant Bioactive Compounds—alkaloids As Nrf2 Inhibitorsmentioning

confidence: 55%

Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer

et al. 2023

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Being a controller of cytoprotective actions, inflammation, and mitochondrial function through participating in the regulation of multiple genes in response to stress-inducing endogenous or exogenous stressors, the transcription factor Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is considered the main cellular defense mechanism to maintain redox balance at cellular and tissue level. While a transient activation of NRF2 protects normal cells under oxidative stress, the hyperactivation of NRF2 in cancer cells may help them to survive and to adapt under oxidative stress. This can be detrimental and related to cancer progression and chemotherapy resistance. Therefore, inhibition of NRF2 activity may be an effective approach for sensitizing cancer cells to anticancer therapy. In this review, we examine alkaloids as NRF2 inhibitors from natural origin, their effects on cancer therapy, and/or as sensitizers of cancer cells to anticancer chemotherapeutics, and their potential clinical applications. Alkaloids, as inhibitor of the NRF2/KEAP1 signaling pathway, can have direct (berberine, evodiamine, and diterpenic aconitine types of alkaloids) or indirect (trigonelline) therapeutic/preventive effects. The network linking alkaloid action with oxidative stress and NRF2 modulation may result in an increased NRF2 synthesis, nuclear translocation, as well in a downstream impact on the synthesis of endogenous antioxidants, effects strongly presumed to be the mechanism of action of alkaloids in inducing cancer cell death or promoting sensitivity of cancer cells to chemotherapeutic agents. In this regard, the identification of additional alkaloids targeting the NRF2 pathway is desirable and the information arising from clinical trials will reveal the potential of these compounds as a promising target for anticancer therapy.

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Section: Plant Bioactive Compounds—alkaloids As Nrf2 Inhibitorsmentioning

confidence: 55%

Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer

et al. 2023

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“…Brusatol (BRU), a quassinoid, isolated from Brucea javanica, has been identified as a potent inhibitor of the Nrf2 signaling pathway [27,28]. In recent years, much evidence has demonstrated that BRU has good anti-tumor activity in different cancers, such as colorectal [29], liver [30,31], lung [32], and pancreatic cancer [33], as well as BC [34]. For example, Lu et al reported that BRU could effectively inhibit the cell viability of colorectal cancer cells HCT116 [35].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Chen et al demonstrated that the synergistic effect of BRU with cisplatin could enhance the antitumor effect on colorectal cancer cells [45]. Xiang et al found that BRU enhanced the anti-tumor effect of gemcitabine by inhibiting the Nrf2 signaling pathway in pancreatic cancer cells [33]. In addition to combination therapy strategies for PD, Zhang et al first showed that combining PD with an inhibitory glycolytic compound, 2-Deoxy-d-glucose (2-DG), inhibited proliferation, migration and invasion and induced apoptosis in MCF7 and 4T1 cells [38].…”

Section: Introductionmentioning

confidence: 99%

Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway

Zhang

Zhu

et al. 2023

IJMS

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Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes Heme Oxygenase-1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.

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Brusatol inhibits the invasion and migration of pancreatic cancer cells by suppressing the NRF2/NF-κB/STAT3 signal cascade

Cited by 2 publications

References 31 publications

Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer

Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer

Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway

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