Menadione reduces <i>CDC25B</i> expression and promotes tumor shrinkage in gastric cancer

Bona, Amanda Braga; Calcagno, Danielle Queiroz; Ribeiro, Helem Ferreira; Muniz, José Augusto Pereira Carneiro; Pinto, Giovanny R.; Rocha, Carlos Alberto Machado da; Junior, Antonio Carlos Cunha Lacreta; Assumpção, Paulo Pimentel de; Herranz, Juan Antonio Rey; Burbano, Rommel Rodrı́guez

doi:10.1177/1756284819895435

Cited by 11 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CDC25B dephosphorylates and activates cyclin-dependent kinase/cyclin complex (CDK1/Cyclin B), which is responsible for cell cycle G2-M transition [ 33 – 36 ]. It has reported that CDC25B inhibitors (vitamin K analogs like adociaquinone B [ 37 ], NSC 663284 [ 38 ], and menadione [ 39 ].) could inhibit CDC25B diphosphatase activity and suppress tumor progression.…”

Section: Introductionmentioning

confidence: 99%

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression

Guo

Wang

et al. 2022

Exp Hematol Oncol

View full text Add to dashboard Cite

Background N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). Methods The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. Results M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. Conclusions METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.

show abstract

Section: Introductionmentioning

confidence: 99%

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression

Guo

Wang

et al. 2022

Exp Hematol Oncol

View full text Add to dashboard Cite

show abstract

“…Menadione has been reported to exhibit anticancer activity in vitro, primarily by generating reactive oxygen species, which lead to DNA damage and cell death (48)(49)(50). Previous studies have demonstrated that in GC, menadione induces cell cycle arrest and apoptosis, and inhibits tumor development and progression in vivo (51)(52)(53). Several clinical trials have evaluated the synergistic cytotoxicity of menadione with other anticancer drugs.…”

Section: A B C Dmentioning

confidence: 99%

Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients

Sun¹,

Zhao²,

Yang³

et al. 2021

J Gastrointest Oncol

View full text Add to dashboard Cite

Background: Gastric cancer (GC) is the most common type of gastrointestinal cancer, and has been studied extensively. However, resistance to chemotherapeutic agents has become a major problem, leading to treatment failure. This study aimed to investigate the molecular mechanisms mediating acquired resistance to cisplatin and fluorouracil (CF) combination-based chemotherapy in GC patients. Methods:The microarray datasets (GSE14209, GSE30070) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using the limma package in R/Bioconductor. Possible targets of the DEMs were predicted using miRWalk, and the putative miRNA-mRNA regulatory network was constructed using Cytoscape software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and proteinprotein interaction (PPI) analyses were then conducted and visualized using the Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape. The prognostic value of hub genes was revealed by Kaplan-Meier Plotter. The causal relationships and interactions between proteins were displayed using DisNor.Finally, similarity analysis was conducted using the Connectivity Map (CMap) profiles to predict a group of small molecules in GC treatment.Results: A total of 394 DEGs and 31 DEMs were identified after analysis of pre-and post-treatment samples of clinical responders to CF therapy. TM9SF4, hsa-miR-185-5p, and hsa-miR-145-5p were found to be critical in the miRNA-mRNA regulatory network. The DEGs were found to be mainly enriched in the processes of ribonucleoprotein complex assembly, catalytic activity acting on RNA, mitochondrial matrix, and thermogenesis. The DEMs were predominantly found to be involved in single-stranded RNA binding and endoplasmic reticulum lumen. HDAC5, DDX17, ILF3, and SDHC were identified as hub genes in the PPI network. Of these, HDAC5, DDX17, and ILF3 were found to be closely related to the overall survival of GC patients. DisNor identified the first neighbors of the key genes. Furthermore, CMap profiles predicted a group of small molecules, including several histone deacetylase inhibitors (HDACIs), menadione, and mibefradil, which could serve as promising therapeutic agents to reverse acquired resistance to CF therapy.Conclusions: Our findings reveal new targets and alternative therapies to overcome the acquired resistance of GC patients to CF treatment.

show abstract

“…The cofactor vitamin K 1 (phylloquinone) undergoes intracellular redox chemistry via its reduction (by nicotinamide adenine dinucleotide, NADH) or epoxidation, essential reactions in blood coagulation, and cell proliferation . The derivative vitamin K 3 (menadione) has shown promising tumor-killing properties . Menadione causes intracellular oxidation via the production of ROS disturbing the intracellular redox balance (oxidative stress-induced cytotoxicity). , …”

Section: Introductionmentioning

confidence: 99%

“…The derivative vitamin K 3 (menadione) has shown promising tumor-killing properties . Menadione causes intracellular oxidation via the production of ROS disturbing the intracellular redox balance (oxidative stress-induced cytotoxicity). , …”

Section: Introductionmentioning

confidence: 99%

“…26 The derivative vitamin K 3 (menadione) has shown promising tumor-killing properties. 27 Menadione causes intracellular oxidation via the production of ROS disturbing the intracellular redox balance (oxidative stress-induced cytotoxicity). 27,28 Here, we report the synthesis and characterization of a series of novel 16-electron Os II half-sandwich complexes (1−16) with the general formula [Os(η 6 -arene)(R-PhDPEN)] (arene = p-cymene or biphenyl, R-PhDPEN = R-substituted phenyl diphenylethylenediamine, Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quinone Reduction by Organo-Osmium Half-Sandwich Transfer Hydrogenation Catalysts

et al. 2021

View full text Add to dashboard Cite

Organo-osmium(II) 16-electron complexes [Os II (η 6arene)(R-PhDPEN)] (where η 6 -arene = para-cymene or biphenyl) can catalyze the reduction of prochiral ketones to optically pure alcohols in the presence of a hydride source. Such complexes can achieve the conversion of pyruvate to unnatural D-lactate in cancer cells. To improve the catalytic performance of these osmium complexes, we have introduced electron-donor and electron-acceptor substituents (R) into the para (R 1 ) or meta (R 2 ) positions of the chiral R-phenyl-sulfonyl-diphenylethylenediamine (R-PhDPEN) ligands and explored the reduction of quinones, potential biological substrates, which play a major role in cellular electron transfer chains. We show that the series of [Os II (η 6arene)(R-PhDPEN)] derivatives exhibit high turnover frequencies, enantioselectivities (>92%), and conversions (>93%) for the asymmetric transfer hydrogenation (ATH) of acetophenone-derived substrates and reduce duroquinone and menadione to their di-alcohol derivatives. Modeling of the catalysis using density functional theory (DFT) calculations suggests a mechanism involving formic acid deprotonation assisted by the catalyst amine groups, phenyl-duroquinone stacking, hydride transfer to Os II , possible CO 2 coordination, and tilting of the η 6 -arene ring, followed by hydride transfer to the quinone. These findings not only reveal subtle differences between Ru(II) and Os(II) catalysts, but also introduce potential biological applications.

show abstract

Menadione reduces CDC25B expression and promotes tumor shrinkage in gastric cancer

Cited by 11 publications

References 40 publications

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression

Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients

Quinone Reduction by Organo-Osmium Half-Sandwich Transfer Hydrogenation Catalysts

Contact Info

Product

Resources

About