Tanshinone IIA inhibits gastric cancer cell stemness through inducing ferroptosis

Ni, Haiwei; Ruan, Guojing; Sun, Chengyi; Yang, Xuan; Miao, Zhenyan; Li, Jifei; Chen, Ying; Qin, Hai; Liu, Yichen; Zheng, Lufeng; Xing, Yingying; Xi, Tao; Li, Xiaoman

doi:10.1002/tox.23388

Cited by 54 publications

(46 citation statements)

References 42 publications

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“…Su (2018) found that Tan-IIA inhibited human gastric cancer AGS cells; one of the molecular mechanisms may be through decreasing the protein expression of VEGFR and HER2, then blocking the Ras/Raf/MEK/ ERK pathway to induce the activation of PARP and caspase-3 to induce apoptosis. 'It is worth mentioning that Ni et al (2022) and Guan et al (2020) pointed out that Tanshinone IIA inhibited the stemness of gastric cancer cells partly by inducing ferroptosis. Chen et al (2017) showed that the tuber of Amorphophallus konjac could increase cell apoptosis and induce cell cycle arrest.…”

Section: Figurementioning

confidence: 99%

Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer

et al. 2022

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Background: Gastric cancer is one of the most important malignancies with poor prognosis. Ferroptosis and cuproptosis are newly discovered metal-dependent types of programmed cell death, which may directly affect the outcome of gastric cancer. Long noncoding RNAs (lncRNAs) can affect the prognosis of cancer with stable structures, which could be potential prognostic prediction factors for gastric cancer.Methods: Differentially expressed metal-dependent programmed cell death (PCD)-related lncRNAs were identified with DESeq2 and Pearson’s correlation analysis. Through GO and KEGG analyses and GSEA , we identified the potential effects of metal-dependent PCD-related lncRNAs on prognosis. Using Cox regression analysis with the LASSO method, we constructed a 12-lncRNA prognostic signature model. Also, we evaluated the prognostic efficiency with Kaplan–Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) methods. The sensitivities for antitumor drugs were then predicted with the pRRophetic method. Also, we discuss Chinese patent medicines and plant extracts that could induce metal-dependent programmed cell death.Results: We constructed a metal-dependent PCD-related lncRNA-gene co-expression network. Also, a metal-dependent PCD-related gastric cancer prognostic signature model including 12 lncRNAs was constructed. The K-M survival curve revealed a poor prognosis in the high-risk group. ROC curve analysis shows that the AUC of our model is 0.766, which is better than that of other published models. Moreover, the half-maximum inhibitory concentration (IC50) for dasatinib, lapatinib, sunitinib, cytarabine, saracatinib, and vinorelbine was much lower among the high-risk group.Conclusion: Our 12 metal-dependent PCD-related lncRNA prognostic signature model may improve the OS prediction for gastric cancer. The antitumor drug sensitivity analysis results may also be helpful for individualized chemotherapy regimen design.

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Section: Figurementioning

confidence: 99%

Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer

et al. 2022

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“…As a widely used TCM compound, TanIIA has already been investigated as a primary or adjuvant therapy with beneficial effects on HNSCC patient survival ( 10 ). The latest studies have confirmed that TanIIA increased the level of lipid peroxides and decreased glutathione levels in gastric cancer cells, both of which are markers of ferroptosis ( 25 ). Guan et al ( 8 ) proved that TanIIA caused decreased intracellular glutathione levels and cysteine levels and increased intracellular reactive oxygen species (ROS) levels.…”

Section: Discussionmentioning

confidence: 94%

Inhibition of cell survival and invasion by Tanshinone IIA via FTH1: A key therapeutic target and biomarker in head and neck squamous cell carcinoma

et al. 2022

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Head and neck squamous cell carcinoma (HNSCC) is a worldwide public health problem; its incidence is increasing and it is now the sixth most common cancer type worldwide. As indicated by existing studies, ferroptosis contributes to HNSCC progression and Tanshinone IIA (TanIIA) may exert therapeutic effects via affecting ferroptosis. However, the underlying mechanisms have remained to be clarified. Therefore, the main aim of the present study was to screen and investigate the key genes in regulating ferroptosis of the human hypopharynx squamous carcinoma cell line FaDu and further elucidate the mechanism of action of TanIIA. A list of ferroptosis-related genes was obtained from the FerrDb database. RNA-sequencing expression (level 3) profiles and corresponding clinical information (cases, n=502; normal controls, n=44) were downloaded from The Cancer Genome Atlas dataset for HNSCC ( https://portal.gdc.com ). The limma package in R software was used to study the differentially expressed mRNAs. Adjusted P<0.05 and Log2(fold change) >1 or <-1 were defined as the threshold for the differential expression of mRNAs. The ClusterProfiler package (version 3.18.0) in R was employed to analyze the Gene Ontology functional terms associated with potential targets and perform a Kyoto Encyclopedia of Genes and Genomes pathway analysis. The R package ggplot2 was used to draw the boxplot and the pheatmap package was used to draw the heatmap. The DEG-related protein-protein interaction network was built with the Search Tool for the Retrieval of Interacting Genes and proteins database and then the visualization was performed using Cytoscape. Ferritin heavy chain 1 (FTH1), transferrin (TF) and TF receptor were screened out using a Wayne diagram, which was drawn by the Venn Diagram package in R. Kaplan-Meier survival analysis and the log-rank test were used to compare differences in survival between the groups. The receiver operating characteristic (v 0.4) (ROC) curve analysis was used to compare the predictive accuracy of mRNAs. FTH1 was screened out and the expression results were verified using The Human Protein Atlas data. Immunohistochemistry and immunofluorescence were used to localize FTH1 expression in FaDu cells. Furthermore, Cell Counting Kit-8 and Transwell assays were used to detect the cell survival and invasion ability, respectively. Furthermore, western blot analysis was performed to analyze protein expression. The results of the present study indicated that three validated ferroptosis marker genes were differentially expressed in HNSCC, among which FTH1 was significantly associated with poorer survival. TanIIA was demonstrated to significantly affect FaDu cell survival and invasiveness and markedly attenuate FTH1 expression. To conclude, the ferroptosis gene FTH1 is highly expressed in HNSCC and TanIIA significantly inhibited HNSCC, partially by suppressing FTH1.

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“…For down-regulated genes by TRPs, ALDH1A1 modulates the activity of lysosomal autophagy inhibitors in cancer cells ( Piao et al, 2017 ). ALDH1A1 was also involved in ferroptosis of gastric cancer ( Ni et al, 2022 ). Aberrant promoter methylation of EFHD1 was highly positive in colorectal cancer plasma samples, and they might be useful in detection of early-stage colorectal cancer ( Takane et al, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

Role of TRPV1 ion channel in cervical squamous cell carcinoma genesis

Wang

Dong

Tian

et al. 2022

Front. Mol. Biosci.

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The transient receptor potential (TRP) family is a widely expressed superfamily of ion channels that regulate intracellular Ca2+ homeostasis and signal transduction. Abnormal expression of TRPV1 is closely related to malignant tumors of the female reproductive system such as breast, ovarian, cervical and endometrial cancers. In this study, we found a significant reduction of TRPV1 expression in cervical squamous cell carcinoma and this expression is inversely association with the risk of cervical squamous cell carcinoma. Furthermore, TRPV1 is involved in cell differentiation, iron death, inflammatory response, and metabolic regulation in cervical squamous cell carcinoma. Meanwhile TRPV1 is positively correlated with T cells and negatively associated with macrophages, indicating that TRPV is associated with tumor cell immunity. Therefore, TRPV1 may be a potential marker of cervical cancer and a promising anti-cancer drug candidate.

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Tanshinone IIA inhibits gastric cancer cell stemness through inducing ferroptosis

Cited by 54 publications

References 42 publications

Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer

Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer

Inhibition of cell survival and invasion by Tanshinone IIA via FTH1: A key therapeutic target and biomarker in head and neck squamous cell carcinoma

Role of TRPV1 ion channel in cervical squamous cell carcinoma genesis

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