Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer

Zhang, Pengfei; Tao, Weiwei; Cai, Lu; Fan, Li; Jiang, Qihang; Yang, Chengbin; Shang, Erxin; Cheng, Haibo; Che, Chun‐Tao; Duan, Jin‐Ao; Zhao, Ming

doi:10.1016/j.phrs.2021.105658

Cited by 19 publications

(17 citation statements)

References 37 publications

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“…Our previous studies revealed the IC 50 values of quassinoids bearing 2‐hydroxy‐acrylketone moiety on MIA PaCa‐2 cells, including brusatol ( 7 ) (0.034 μM), bruceine A ( 8 ) (0.029 μM), bruceantinol ( 9 ) (0.669 μM), bruceine B ( 12 ) (0.065 μM), and bruceantin ( 13 ) (0.781 μM) [9,27] . These findings have aroused our interest in hunting for other quassinoids as anti‐pancreatic cancer leads.…”

Section: Resultsmentioning

confidence: 93%

A New C22‐Quassinoid with Anti‐Pancreatic Adenocarcinoma Activity from Seeds of Brucea javanica

Yang

et al. 2022

Chemistry & Biodiversity

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An undescribed C22‐quassinoid named sergeolide A (1) and fifteen known quassinoids (2–16) were obtained from the seeds of Brucea javanica (Simaroubaceae). All chemical structures were established based on spectroscopic data and X‐ray diffraction analysis. Sergeolide A (1) is the first example of a naturally occurring C22‐quassinoid bearing a butenolide group fused the A ring of the bruceolide skeleton from Brucea genus. And this is the first report of the NMR data for desmethyl‐bruceines B (2) and C (3) and the crystal structure for bruceolide (11). In addition, all isolates were evaluated for their anti‐pancreatic adenocarcinoma activity by measuring the growth inhibitory of the MIA PaCa‐2 cell lines. Consequently, compounds 1, 7–10, and 12–16 exhibited potent anti‐pancreatic cancer activity in vitro (IC50=0.054∼0.357 μM).

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Section: Resultsmentioning

confidence: 93%

A New C22‐Quassinoid with Anti‐Pancreatic Adenocarcinoma Activity from Seeds of Brucea javanica

Yang

et al. 2022

Chemistry & Biodiversity

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“…Changes in cell number and growth may also be related to the occurrence of cell apoptosis 39 . Annexin V‐FITC and PI‐CY3 were used to detect cell apoptosis by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…Changes in cell number and growth may also be related to the occurrence of cell apoptosis. 39 Annexin V-FITC and PI-CY3 were used to detect cell apoptosis by flow cytometry. As the results shows in Figure 5A,B, that CDK5RAP3 deficiency caused a 19.8% reduction in live cells in MEFs (93 ± 1.56% vs. 73.2 ± 1.72%, p < 0.01; Figure 5A) and 2.5% reduction in live cells in MCF7 (97.3 ± 0.42% vs. 94.8 ± 0.51%, p < 0.01; Figure 5B).…”

Section: Cdk5rap3 Deficiency Promoted Apoptosismentioning

confidence: 99%

CDK5RAP3, an essential regulator of checkpoint, interacts with RPL26 and maintains the stability of cell growth

Yan

Ali

et al. 2022

Cell Proliferation

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Purpose and Materials: CDK5RAP3 (CDK5 regulatory subunit associated protein 3) was originally identified as a binding protein of CDK5. It is a crucial gene controlling biological functions, such as cell proliferation, apoptosis, invasion, and metastasis.Although previous studies have also shown that CDK5RAP3 is involved in a variety of signalling pathways, however, the mechanism of CDK5RAP3 remains largely undefined. This study utilized MEFs from conditional knockout mice to inhibit CDK5RAP3 and knockdown CDK5RAP3 in MCF7 to explore the role of CDK5RAP3 in cell growth, mitosis, and cell death.Results: CDK5RAP3 was found to be widely distributed throughout the centrosome, spindle, and endoplasmic reticulum, indicating that it is involved in regulating a variety of cellular activities. CDK5RAP3 deficiency resulted in instability of cell growth.CDK5RAP3 deficiency partly blocks the cell cycle in G 2 /M by downregulating CDK1 (Cyclin-dependent kinase 1) and CCNB1 (Cyclin B1) expression levels. The cell proliferation rate was decreased, thereby slowing down the cell growth rate. Furthermore, the results showed that CDK5RAP3 interacts with RPL26 (ribosome protein L26) to regulate the mTOR pathway. CDK5RAP3 and RPL26 deficiency inhibited mTOR/p-mTOR protein and induce autophagy, resulting in an upregulation of the percentage of apoptosis, and the upregulated percentage of apoptosis also slowed cell growth. Conclusions:Our experiments show that CDK5RAP3 interacts with RPL26 and maintains the stability of cell growth. It shows that CDK5RAP3 plays an important role in cell growth and can be used as the target of gene medicine.

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“…In the past decades, many strategies have been developed to excavate and investigate the potential inhibitors of proteins. For example, HuProt™20K microarray chip is a solid-phase protein array chip with nearly 20, 000 full-length proteins on the chip, providing an unbiased high-throughput screening method to discover targets of molecules [ 23 , 24 ]. Molecular dynamics simulations of proteins, which have been used for 25 years ago, are by now widely used as strategies to investigate structure and dynamics under a variety of conditions [ 25 – 27 ].…”

Section: Introductionmentioning

confidence: 99%

Emodin Ameliorates Intestinal Dysfunction by Maintaining Intestinal Barrier Integrity and Modulating the Microbiota in Septic Mice

Zhang

Lian

Zhang

et al. 2022

Mediators of Inflammation

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Sepsis-induced inflammatory response leads to intestinal damage and secondary bacterial translocation, causing systemic infections and eventually death. Emodin is a natural anthraquinone derivative in many plants with promising bioactivities. However, the effects and mechanisms of emodin on sepsis-induced intestinal dysfunctions have not been well clarified yet. We found that emodin treatment suppressed the inflammatory response in the intestines of septic mice. Intestinal barrier function was also improved by emodin through enhancing ZO-1 and occludin expression, which prevented the secondary translocation of Escherichia coli. By proteome microarray investigation, JNK2 was identified as a direct target of emodin. In vitro study also showed that emodin inhibited LPS-induced inflammatory response in intestinal epithelial cells. Nuclear factors including NF-κB and AP-1 were further identified as downstream effectors of JNK2. Bioinformatic analysis based on 16s rRNA gene sequencing illustrated that emodin treatment significantly increased the alpha- and beta-diversity of gut microbiota in septic mice. Moreover, data according to functional prediction showed that emodin decreased the abundance of potential pathogenic bacteria in gut. Our findings have shown that emodin treatment prevented inflammatory induced barrier dysfunction and decreased the potential pathogenicity of lumen bacteria, reducing the hazard of lumen bacterial translocation during sepsis.

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Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer

Cited by 19 publications

References 37 publications

A New C22‐Quassinoid with Anti‐Pancreatic Adenocarcinoma Activity from Seeds of Brucea javanica

A New C22‐Quassinoid with Anti‐Pancreatic Adenocarcinoma Activity from Seeds of Brucea javanica

CDK5RAP3, an essential regulator of checkpoint, interacts with RPL26 and maintains the stability of cell growth

Emodin Ameliorates Intestinal Dysfunction by Maintaining Intestinal Barrier Integrity and Modulating the Microbiota in Septic Mice

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