Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas

Wu, Zerui; Xu, Yunqiu; Xu, Jing; Lu, Jianglong; Cai, Lin; Li, Qun; Wang, Chengde; Su, Zhipeng

doi:10.1155/2021/6696015

Cited by 11 publications

(9 citation statements)

References 39 publications

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“…In agreement with our findings, a study conducted on NSCLC cells revealed a possible association between brusatol and the modulation of ROS-mediated mitochondrial-dependent pathways together with the inhibition of an antioxidant response mediated by NRF2 inhibition [ 12 ]. In another study, the promotion of ROS and NRF2 suppression by brusatol resulted in a growth inhibition of lung cancer and pituitary cancer cells both in vitro and in vivo [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation

et al. 2022

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Acute lymphoblastic leukemia (ALL) is one of the most common hematological malignancies at pediatric ages and is characterized by different chromosomal rearrangements and genetic abnormalities involved in the differentiation and proliferation of lymphoid precursor cells. Brusatol is a quassinoid plant extract extensively studied due to its antineoplastic effect through global protein synthesis and nuclear factor erythroid 2-related factor-2 (NRF2) signaling inhibition. NRF2 is the main regulator of cellular antioxidant response and reactive oxygen species (ROS), which plays an important role in oxidative stress regulation. This study aimed to evaluate the effect of brusatol in in vitro models of ALL. KOPN-8 (B-ALL), CEM (T-ALL), and MOLT-4 (T-ALL) cell lines were incubated with increasing concentrations of brusatol, and the metabolic activity was evaluated using the resazurin assay. Flow cytometry was used to evaluate cell death, cell cycle, mitochondrial membrane potential (Δψmit), and to measure ROS and reduced glutathione (GSH) levels. Our results show that brusatol promoted a decrease in metabolic activity in ALL cell lines in a time-, dose-, and cell-line-dependent manner. Brusatol induced a cytostatic effect by cell cycle arrest in G0/G1 in all cell lines; however, cell death mediated by apoptosis was only observed in T-ALL cells. Brusatol leads to an oxidative stress imbalance by the increase in ROS levels, namely, superoxide anion. Redox imbalance and cellular apoptosis induced by brusatol are highly modulated by mitochondria disruption as a decrease in mitochondrial membrane potential is detected. These data suggest that brusatol might represent a new therapeutic approach for acute lymphoblastic leukemia, particularly for ALL T-cell lineage.

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Section: Discussionmentioning

confidence: 99%

Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation

et al. 2022

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“…Previous studies have shown that the inhibition of the mTORC1 pathway is involved in the inhibition of PitNET growth [39]. The Brusatol-induced inhibition of the mTORC1 signaling pathway leads to inhibition of tumor growth in PitNETs [40]. Rapamycin and RAD001, which are mTOR inhibitors, potently inhibit pituitary cell proliferation in GH3 cells [41].…”

Section: Discussionmentioning

confidence: 99%

MiR-320a Acts as a Tumor Suppressor in Somatotroph Pituitary Neuroendocrine Tumors by Targeting BCAT1

Zhao,

Li,

Gao

et al. 2023

Neuroendocrinology

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Introduction: Aberrant miR-320a has been reported to be involved in the tumorigenesis of several cancers. In our previous study, we identified the low expression of circulating miR-320a in patients with somatotroph pituitary neuroendocrine tumor (PitNET); however, the role of miR-320a in somatotroph PitNET proliferation is still unclear. Methods: Cell viability and colony formation assays were used to detect the effect of miR-320a and BCAT1 on GH3 cells. TargetScan was used to identify the target genes of miR-320a. Dual-luciferase reporter gene assay was used to explore the relation between miR-320a and BCAT1. Transcriptome and proteome analyses were performed between somatotroph PitNETs and healthy controls. The expression level of miR-320a in somatotroph PitNETs were detected by RT-qPCR and Western blot. Results: miR-320a mimics inhibit cell proliferation, while miR-320a inhibitors promote cell proliferation in GH3 cells. An overlap analysis using a Venn diagram revealed that BCAT1 is the only target gene of miR-320a overexpressed in somatotroph PitNETs compared to healthy controls, as revealed by both microarray and proteomics results. A dual-luciferase reporter gene assay showed that miR-320a may bind to the BCAT1-3′UTR. The transfection of miR-320a mimics downregulated the expression and miR-320a inhibitors and upregulated the expression of BCAT1 in GH3 cells. The interference of BCAT1 expression in GH3 cells downregulated cell proliferation and growth. Pan-cancer analyses demonstrated that high BCAT1 expression often indicates a poor prognosis. Conclusion: Our findings illustrate that miR-320a may function as a tumor suppressor and BCAT1 may promote tumor progression. miR-320a may inhibit the growth of somatotroph PitNETs by targeting BCAT1.

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“…In several studies, Bru was considered as an unparalleled inhibitor of the Nrf2 pathway, exhibiting growth inhibition and pro-apoptotic effects in a variety of cancer cells ( Evans et al, 2018 ; Cai et al, 2019 ). By promoting ROS production and down-regulating Nrf2 expression, Bru significantly inhibited the growth of lung cancer and pituitary tumor cells in vitro and in vivo ( Sun et al, 2016 ; Wu et al, 2021 ). Similar results were also shown in the field of glioma treatment ( Tang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1

et al. 2021

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Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

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Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas

Cited by 11 publications

References 39 publications

Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation

Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation

MiR-320a Acts as a Tumor Suppressor in Somatotroph Pituitary Neuroendocrine Tumors by Targeting BCAT1

Brusatol Inhibits Proliferation and Invasion of Glioblastoma by Down-Regulating the Expression of ECM1

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