ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer

Tao, Shuixiang; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

doi:10.3892/mmr.2017.6141

Cited by 9 publications

(6 citation statements)

References 23 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings showed that most of the cells were significantly arrested on the phase S, upon Br-Ell-SO 3 Na treatment at both 35 µM and 70 µM doses. As mentioned earlier, the anticancer potential of ellipticine and its derivatives has already been reported elsewhere, but usually those substances induce the cell arrest at the phase G2 of the cell cycle [26][27][28]. Our data demonstrated that the mechanism of action of Br-Ell-SO 3 Na on the cell cycle differs from previously reported ellipticine derivatives.…”

Section: Discussionsupporting

confidence: 71%

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

et al. 2020

View full text Add to dashboard Cite

Cancer still remains a major public health concern around the world and the search for new potential antitumor molecules is essential for fighting the disease. This study evaluated the anticancer and immunomodulatory potential of the newly synthetized ellipticine derivate: sodium bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate (Br-Ell-SO3Na). It was prepared by the chlorosulfonation of 9-bromoellipticine. The ellipticine-7-sulfonic acid itself is not soluble, but its saponification with sodium hydroxide afforded a water-soluble sodium salt. The cytotoxicity of Br-Ell-SO3Na was tested against cancerous (K562 cell line) and non-cancerous cells (Vero cell line and human peripheral blood mononuclear cells (PBMC)) using a Methylthiazoletetrazolium (MTT) assay. Cell cycle arrest was assessed by flow cytometry and the immunomodulatory activity was analyzed through an enzyme-linked immunosorbent assay (ELISA). The results showed that the Br-Ell-SO3Na molecule has specific anticancer activity (IC50 = 35 µM) against the K562 cell line, once no cytotoxicity effect was verified against non-cancerous cells. Cell cycle analysis demonstrated that K562 cells treated with Br-Ell-SO3Na were arrested in the phase S. Moreover, the production of IL-6 increased and the expression of IL-8 was inhibited in the human PBMC treated with Br-Ell-SO3Na. The results demonstrated that Br-Ell-SO3Na is a promising anticancer molecule attested by its noteworthy activity against the K562 tumor cell line and immunomodulatory activity in human PBMC cells.

show abstract

Section: Discussionsupporting

confidence: 71%

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The tumor suppressor p53 plays an essential role in many malignancies, including promoting progression of BCa [ 99 , 100 , 101 , 102 ]. Dueñas et al found that mutations in the TP53 gene and epigenetically mediated increased p53 protein expression favor the progression and recurrence of non-muscle invasive bladder cancer (NMIBC).…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer

Zhang

Berndt‐Paetz

Neuhaus

2021

Cancers

View full text Add to dashboard Cite

Background: A hallmark of Notch signaling is its variable role in tumor biology, ranging from tumor-suppressive to oncogenic effects. Until now, the mechanisms and functions of Notch pathways in bladder cancer (BCa) are still unclear. Methods: We used publicly available data from the GTEx and TCGA-BLCA databases to explore the role of the canonical Notch pathways in BCa on the basis of the RNA expression levels of Notch receptors, ligands, and downstream genes. For statistical analyses of cancer and non-cancerous samples, we used R software packages and public databases/webservers. Results: We found differential expression between control and BCa samples for all Notch receptors (NOTCH1, 2, 3, 4), the delta-like Notch ligands (DLL1, 3, 4), and the typical downstream gene hairy and enhancer of split 1 (HES1). NOTCH2/3 and DLL4 can significantly differentiate non-cancerous samples from cancers and were broadly altered in subgroups. High expression levels of NOTCH2/3 receptors correlated with worse overall survival (OS) and shorter disease-free survival (DFS). However, at long-term (>8 years) follow-up, NOTCH2 expression was associated with a better OS and DFS. Furthermore, the cases with the high levels of DLL4 were associated with worse OS but improved DFS. Pathway network analysis revealed that NOTCH2/3 in particular correlated with cell cycle, epithelial–mesenchymal transition (EMT), numbers of lymphocyte subtypes, and modulation of the immune system. Conclusions: NOTCH2/3 and DLL4 are potential drivers of Notch signaling in BCa, indicating that Notch and associated pathways play an essential role in the progression and prognosis of BCa through directly modulating immune cells or through interaction with cell cycle and EMT.

show abstract

“…Biological pathways of four significant modules from PPI network analysis using Cytoscape contained "cell cycle, mitotic", "epithelial to mesenchymal transition" (EMT), "ErbB receptor signaling" and "neuronal system" (Figure 3). Of note, "cell cycle" and "p53 signaling pathways" directly modulate the cell cycle in many cancers, and are an inevitable theme in cancer research [38,39]. Tumor suppressor p53 is the most frequently mutated gene in human cancer [40].…”

Section: Biological Progression Potentially Associated With Bcamentioning

confidence: 99%

Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

2020

View full text Add to dashboard Cite

Bladder cancer (BCa) is one of the most common malignancies and has a relatively poor outcome worldwide. However, the molecular mechanisms and processes of BCa development and progression remain poorly understood. Therefore, the present study aimed to identify candidate genes in the carcinogenesis and progression of BCa. Five GEO datasets and TCGA-BLCA datasets were analyzed by statistical software R, FUNRICH, Cytoscape, and online instruments to identify differentially expressed genes (DEGs), to construct protein‒protein interaction networks (PPIs) and perform functional enrichment analysis and survival analyses. In total, we found 418 DEGs. We found 14 hub genes, and gene ontology (GO) analysis revealed DEG enrichment in networks and pathways related to cell cycle and proliferation, but also in cell movement, receptor signaling, and viral carcinogenesis. Compared with noncancerous tissues, TPM1, CRYAB, and CASQ2 were significantly downregulated in BCa, and the other hub genes were significant upregulated. Furthermore, MAD2L1 and CASQ2 potentially play a pivotal role in lymph nodal metastasis. CRYAB and CASQ2 were both significantly correlated with overall survival (OS) and disease-free survival (DFS). The present study highlights an up to now unrecognized possible role of CASQ2 in cancer (BCa). Furthermore, CRYAB has never been described in BCa, but our study suggests that it may also be a candidate biomarker in BCa.

show abstract

ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer

Cited by 9 publications

References 23 publications

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer

Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

Contact Info

Product

Resources

About