Identification of natural compounds targeting Annexin A2 with an anti-cancer effect

Wang, Yushi; Li, He; Li, Yang; Zhu, Hongyan

doi:10.1007/s13238-018-0513-z

Cited by 37 publications

(24 citation statements)

References 39 publications

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“…that ANXA2 promotes NF‐κB activation by binding to NF‐κB p50 subunit with its N terminal sequences, increasing its transcriptional activity and upregulating the transcription of several target genes downstream of NF‐κB, including interleukin (IL)‐6, which contributes to anti‐apoptotic signalling (Jung et al., 2015). Wang et al., in 2018, demonstrated that two ginsenosides Rg5 (G‐Rg5) and Rk1 (G‐Rk1), with similar structure, directly bound to ANXA2 (Wang et al., 2018), inhibiting its interaction with the NF‐κB p50 subunit and leading to caspase activation and apoptosis. These studies demonstrated that inhibition of ANXA2 provided a new regulatory tool on NF‐κB activity and supported the notion that the inhibition of ANXA2 may be a suitable anti‐cancer therapy (Wang et al., 2018).…”

Section: Annexin A2 (Anxa2)mentioning

confidence: 99%

“…Wang et al., in 2018, demonstrated that two ginsenosides Rg5 (G‐Rg5) and Rk1 (G‐Rk1), with similar structure, directly bound to ANXA2 (Wang et al., 2018), inhibiting its interaction with the NF‐κB p50 subunit and leading to caspase activation and apoptosis. These studies demonstrated that inhibition of ANXA2 provided a new regulatory tool on NF‐κB activity and supported the notion that the inhibition of ANXA2 may be a suitable anti‐cancer therapy (Wang et al., 2018).…”

Section: Annexin A2 (Anxa2)mentioning

confidence: 99%

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RNA packaging into extracellular vesicles: An orchestra of RNA‐binding proteins?

Fabbiano

Corsi

Gurrieri

et al. 2020

J of Extracellular Vesicle

178

149

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Extracellular vesicles (EVs) are heterogeneous membranous particles released from the cells through different biogenetic and secretory mechanisms. We now conceive EVs as shuttles mediating cellular communication, carrying a variety of molecules resulting from intracellular homeostatic mechanisms. The RNA is a widely detected cargo and, impressively, a recognized functional intermediate that elects EVs as modulators of cancer cell phenotypes, determinants of disease spreading, cell surrogates in regenerative medicine, and a source for non‐invasive molecular diagnostics. The mechanistic elucidation of the intracellular events responsible for the engagement of RNA into EVs will significantly improve the comprehension and possibly the prediction of EV “quality” in association with cell physiology. Interestingly, the application of multidisciplinary approaches, including biochemical as well as cell‐based and computational strategies, is increasingly revealing an active RNA‐packaging process implicating RNA‐binding proteins (RBPs) in the sorting of coding and non‐coding RNAs. In this review, we provide a comprehensive view of RBPs recently emerging as part of the EV biology, considering the scenarios where: (i) individual RBPs were detected in EVs along with their RNA substrates, (ii) RBPs were detected in EVs with inferred RNA targets, and (iii) EV‐transcripts were found to harbour sequence motifs mirroring the activity of RBPs. Proteins so far identified are members of the hnRNP family (hnRNPA2B1, hnRNPC1, hnRNPG, hnRNPH1, hnRNPK, and hnRNPQ), as well as YBX1, HuR, AGO2, IGF2BP1, MEX3C, ANXA2, ALIX, NCL, FUS, TDP‐43, MVP, LIN28, SRP9/14, QKI, and TERT. We describe the RBPs based on protein domain features, current knowledge on the association with human diseases, recognition of RNA consensus motifs, and the need to clarify the functional significance in different cellular contexts. We also summarize data on previously identified RBP inhibitor small molecules that could also be introduced in EV research as potential modulators of vesicular RNA sorting.

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Section: Annexin A2 (Anxa2)mentioning

confidence: 99%

Section: Annexin A2 (Anxa2)mentioning

confidence: 99%

RNA packaging into extracellular vesicles: An orchestra of RNA‐binding proteins?

Fabbiano

Corsi

Gurrieri

et al. 2020

J of Extracellular Vesicle

178

149

View full text Add to dashboard Cite

show abstract

“…Additionally, the expression levels of procaspase-8 and −9 decreased after the carriers-mediated Dz13 transfection, suggesting the activation of caspase-8 and −9 through the cleavage of their precursors. Basically, the activation of caspase-8 has been identified to play a critical role in the cell apoptosis through the death receptor-dependent pathway, while caspase-9 could initiate the cell apoptosis based on the mitochondria-dependent apoptotic pathway 39,40. Thus, we inferred that the carrier-mediated Dz13 transfection could trigger the cell apoptosis through both death receptor-dependent pathway and mitochondrial apoptotic signaling pathway.…”

Section: Resultsmentioning

confidence: 85%

<p>Inhibition of proliferation and migration of tumor cells through phenylboronic acid-functionalized polyamidoamine-mediated delivery of a therapeutic DNAzyme Dz13</p>

Yang¹,

Zhang²,

Xing³

et al. 2019

IJN

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Background The phenylboronic acid-functionalized polyamidoamine (PP) was employed as a gene carrier for Dz13 delivery, inducing an obvious anticancer response. Materials and methods The Dz13 condensation ability of PP was evaluated through gel retardation assay. The cellular uptake mechanism of PP/Dz13 nanoparticles was studied using confocal laser scanning microscope and flow cytometer. The inhibition ability of cell proliferation, migration and invasion was investigated through MTT assay, flow cytometry, wound healing and Transwell migration assays, using hepatocarcinoma cell line HepG2 as a model. Finally, Western blotting analysis was used to detect the signaling pathway associated with the inhibition of cell apoptosis and migration induced by Dz13 delivery. Results The carrier PP could efficiently condense Dz13 into stable nanoparticles at mass ratios of >1.5. The hydrodynamic diameter and zeta potential of PP/Dz13 nanoparticles were measured to be 204.77 nm and +22.00 mV at a mass ratio of 10.0, respectively. The nanoparticles could realize an efficient cellular uptake in sialic acid-dependent endocytosis manner. Moreover, the nanoparticles exhibited an obvious antiproliferation effect through the induction of cell apoptosis and cell cycle arrest due to the cleavage of c-Jun mRNA. Besides, the suppression of cell migration and invasion could be achieved after the PP/Dz13 transfection, attributing to the decreased expression level of MMP-2 and MMP-9 . Conclusion The PP provided a potential delivery system to achieve the tumor-targeting gene therapy.

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“…Thus, it was possible that C-K–induced downregulation of NF-кB activity was mainly mediated by Annexin A2. We have previously indicated that (20S)G-Rh2, G-Rg5, and G-Rk1 inhibited NF-κB activation targeting Annexin A2; however, a similar mechanism was not obtained to other ginsenosides such as (20S/R)G-Rg3, (20R)G-Rh2, protopanoxadiol (PPD), and protopanaxatriol (PPT) (data not shown) [25], [30]. These researches suggested that C-K acted as a specific binding molecule to Annexin A2.…”

Section: Discussionmentioning

confidence: 95%

Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2

Wang

Zhu

et al. 2019

Journal of Ginseng Research

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Background Ginsenoside compound K(C-K), a major metabolite of ginsenoside, exhibits anticancer activity in various cancer cells and animal models. A cell signaling study has shown that C-K inhibited nuclear factor-kappa B (NF-κB) pathway in human astroglial cells and liver cancer cells. However, the molecular targets of C-K and the initiating events were not elucidated. Methods Interaction between C-K and Annexin A2 was determined by molecular docking and thermal shift assay. HepG2 cells were treated with C-K, followed by a luciferase reporter assay for NF-кB, immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-кB p50 subunit, coimmunoprecipitation of Annexin A2 and NF-кB p50 subunit, and both cell viability assay and plate clone formation assay to determine the cell viability. Results Both molecular docking and thermal shift assay positively confirmed the interaction between Annexin A2 and C-K. This interaction prevented the interaction between Annexin A2 and NF-кB p50 subunit and their nuclear colocalization, which attenuated the activation of NF-кB and the expression of its downstream genes, followed by the activation of caspase 9 and 3. In addition, the overexpression of Annexin A2-K320A, a C-K binding-deficient mutant of Annexin A2, rendered cells to resist C-K treatment, indicating that C-K exerts its cytotoxic activity mainly by targeting Annexin A2. Conclusion This study for the first time revealed a cellular target of C-K and the molecular mechanism for its anticancer activity.

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Identification of natural compounds targeting Annexin A2 with an anti-cancer effect

Cited by 37 publications

References 39 publications

RNA packaging into extracellular vesicles: An orchestra of RNA‐binding proteins?

RNA packaging into extracellular vesicles: An orchestra of RNA‐binding proteins?

<p>Inhibition of proliferation and migration of tumor cells through phenylboronic acid-functionalized polyamidoamine-mediated delivery of a therapeutic DNAzyme Dz13</p>

Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2

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