Xanthium strumarium´s xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells

Piloto-Ferrer, Janet; Sánchez-Lamar, Ángel; Francisco, Marbelis; González, Maria L.; Merino, Nelsón; Aparicio, Guillermo; Pérez, Carlos L; Rodeiro, Idania; Lopes, Míriam Teresa Paz

doi:10.1016/j.phymed.2018.12.019

Cited by 16 publications

(8 citation statements)

References 38 publications

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“…Previous research has shown that altered expression of particular genes may affect ESCC cell metastasis, invasion, apoptosis and proliferation [15][16][17] . Our results agree with the fact that carcinoma cell metastasis and invasion are closely associated with abnormal cell adhesion, endodermal cell division and nuclear division [18][19][20] . Extracellular matrix (ECM), is a critical component of the cancer cell niche, it can provide the tissue with the mechanical support and also mediate the cell-microenvironment interactions 21,22 .…”

Section: Discussionsupporting

confidence: 92%

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Han

Yang

Hosseini

et al. 2020

Sci Rep

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Aberrant methylated genes (DMGs) play an important role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). In this study, we aimed to integrate three cohorts profile datasets to ascertain aberrant methylated-differentially expressed genes and pathways associated with ESCC by comprehensive bioinformatics analysis. We downloaded data of gene expression microarrays (GSE20347, GSE38129) and gene methylation microarrays (GSE52826) from the Gene Expression Omnibus (GEO) database. Aberrantly differentially expressed genes (DEGs) were obtained by GEO2R tool. The David database was then used to perform Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses on selected genes. STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network, then the modules in the PPI networks were analyzed with MCODE and the hub genes chose from the PPI networks were verified by Oncomine and TCGA database. In total, 291 hypomethylation-high expression genes and 168 hypermethylation-low expression genes were identified at the screening step, and finally found six mostly changed hub genes including KIF14, CDK1, AURKA, LCN2, TGM1, and DSG1. Pathway analysis indicated that aberrantly methylated DEGs mainly associated with the P13K-AKT signaling, cAMP signaling and cell cycle process. After validation in multiple databases, most hub genes remained significant. Patients with high expression of AURKA were associated with shorter overall survival. To summarize, we have identified six feasible aberrant methylated-differentially expressed genes and pathways in ESCC by bioinformatics analysis, potentially providing valuable information for the molecular mechanisms of ESCC. Our data combined the analysis of gene expression profiling microarrays and gene methylation profiling microarrays, simultaneously, and in this way, it can shed a light for screening and diagnosis of ESCC in future. Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, with incidence rates ranking fourth and eighth in China and worldwide, respectively 1,2. ESCC is a serious threat to human health, and its five-year survival rate is less than 10%, making it a leading cause of cancer-related death 3. So far,

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Section: Discussionsupporting

confidence: 92%

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Han

Yang

Hosseini

et al. 2020

Sci Rep

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“…Xanthatin, as a traditional sesquiterpene lactone compound, can produce certain cytotoxic effects and has good biological activity. Studies have reported that xanthatin can produce anticancer activities by inducing cell cycle arrest, apoptosis and DNA damage (Ma et al, 2020; Piloto‐Ferrer et al, 2019; Tao et al, 2017). Our research found that xanthatin can effectively inhibit the migration and invasion of human colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Xanthatin inhibits human colon cancer cells progression via mTOR signaling mediated energy metabolism alteration

Liu

Xie

et al. 2021

Drug Development Research

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Tumor cells exhibit higher glycolysis and rely on abnormal energy metabolism to produce ATP, which is essential for cell proliferation and migration. Abnormal energy metabolism inhibition is considered a promising tumor treatment strategy. Xanthatin is an active sesquiterpene lactone isolated from Xanthium strumarium L. This study evaluated the effect of xanthatin on the energy metabolism of human colon cancer cells. The results showed that xanthatin significantly inhibited the migration and invasion of human HT‐29 and HCT‐116 colon cancer cells. We found that xanthatin effectively reduced the production of ATP and promoted the accumulation of lactate. Xanthatin inhibited glycolysis which may be related to the reduction of glucose transporter 1 (Glut1) and monocarboxylate transporter 4 (MCT4) mRNA and protein levels. Concomitantly, xanthatin promoted complex II activity and oxidative phosphorylation (OXPHOS), resulting in mitochondrial damage and cell death in HT‐29 cells. Furthermore, xanthatin inhibited the phosphorylation of mTOR, the phosphorylation of 4E‐binding protein 1 (4E‐BP1) and c‐myc in HT‐29 cells. Moreover, rapamycin, a mTOR inhibitor, could enhance the cytotoxicity effect in xanthatin treated HT‐29 cells. Additionally, HT‐29 cells transfected with si‐mTOR aggravated xanthatin induced cell viability inhibition. Based on these results, we observed that the effect of xanthatin on energy metabolism may be related to its inhibition of the mTOR signaling pathway. Collectively, this study provides important insights into xanthatin's anticancer effect, which occurs by regulation of the energy metabolism of human colon cancer cells, and suggest that xanthatin has potential as a botanical drug against abnormal tumor energy metabolism.

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“…Xanthatin has been shown to effectively inhibit the proliferation of many cancer cells, such as melanoma cells, lung cancer cells, and hepatocellular carcinoma cells. 29 – 35 By using differential cytotoxic drug screening, we discovered that xanthatin arrested cell cycle progression and induced apoptosis in retinoblastoma cells by suppressing the PLK1-mediated G2/M cell cycle pathway. Remarkably, xanthatin is an outstanding sesquiterpene lactone compound with impressive antitumor activity that exhibits little toxicity in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle

Yang

Zong

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Purpose Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, making the development of targeted therapy an urgent need. Therefore, we intended to find a potential drug for human retinoblastoma by screening an in-house compound library that included 89 purified and well-characterized natural products. Methods We screened a panel of 89 natural products in retinoblastoma cell lines to find the inhibitor. The inhibition of the identified inhibitor xanthatin on cell growth was detected through half-maximal inhibitory concentration (IC 50 ), flow cytometry assay, and zebrafish model system. RNA-seq further selected the target gene PLK1. Results We reported the discovery of xanthatin as an effective inhibitor of retinoblastoma. Mechanistically, xanthatin selectively inhibited the proliferation of retinoblastoma cells by inducing cell cycle arrest and promoting apoptosis. Interestingly, xanthatin targeted PLK1-mediated cell cycle progression. The efficacy of xanthatin was further confirmed in zebrafish models. Conclusions Collectively, our data suggested that xanthatin significantly inhibited tumor growth in vitro and in vivo, and xanthatin could be a potential drug treatment for retinoblastoma.

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Xanthium strumarium´s xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells

Cited by 16 publications

References 38 publications

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Xanthatin inhibits human colon cancer cells progression via mTOR signaling mediated energy metabolism alteration

Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle

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