Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway

Xiao, Xue; Guo, Le; Dai, Weiyou; Yan, Bo; Zhang, Jin; Yuan, Qiang; Zhou, Li; Shan, Letian; Efferth, Thomas

doi:10.1016/j.jep.2022.115167

Cited by 20 publications

(18 citation statements)

References 59 publications

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“…Moreover, the genetic interaction between the BRAF and p53 pathways leads to melanoma development. Similar dependency of these two pathways was observed in ZF with non-small cell lung carcinoma [ 16 ] and osteosarcoma [ 17 ]. CFTR (cystic fibrosis transmembrane conductance regulator) is involved in Wnt-dependent hematopoiesis, which interacts with adherens junction molecule AF-6/afadin via PDZBD (PDZ binding domain), thus regulating epithelial polarity and affecting cancer metastasis [ 100 ].…”

Section: Aim Of the Studies—what Is The Point?supporting

confidence: 68%

“…KSHV (Kaposi’s sarcoma-associated herpesvirus)-infected PEL (primary effusion lymphoma) cells injected into the yolk sac of larvae indicated proliferation and the embryos tolerated xenotransplantation [ 15 ]. Non-small cell lung cancer (NSCLC) H1299 (p53-deficient) and A549 (p53-wild type) cell lines were xenografted into larval stage [ 16 ], as well as osteosarcoma (U2-OS) cells [ 17 ]. Another transplantation method used Matrigel as a cell matrix.…”

Section: Disease Induction: How To Create a Fish Modelmentioning

confidence: 99%

“…A new, interesting direction in cancer research is testing the anticancer potential of newly discovered plant compounds. A theabrownin derived from green tea treatment caused the suppression of human non-small cell lung carcinoma when tested in a zebrafish xenograft [ 16 ]. Another interesting plant is Radix Salviae miltiorrhizae (also called Danshen in traditional Chinese medicine) containing tanshinol.…”

Section: Aim Of the Studies—what Is The Point?mentioning

confidence: 99%

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One Host-Multiple Applications: Zebrafish (Danio rerio) as Promising Model for Studying Human Cancers and Pathogenic Diseases

Dudziak

Nowak

Sozoniuk

2022

IJMS

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In recent years, zebrafish (ZF) has been increasingly applied as a model in human disease studies, with a particular focus on cancer. A number of advantages make it an attractive alternative for mice widely used so far. Due to the many advantages of zebrafish, modifications can be based on different mechanisms and the induction of human disease can take different forms depending on the research goal. Genetic manipulation, tumor transplantation, or injection of the pathogen are only a few examples of using ZF as a model. Most of the studies are conducted in order to understand the disease mechanism, monitor disease progression, test new or alternative therapies, and select the best treatment. The transplantation of cancer cells derived from patients enables the development of personalized medicine. To better mimic a patient’s body environment, immune-deficient models (SCID) have been developed. A lower immune response is mostly generated by genetic manipulation but also by irradiation or dexamethasone treatment. For many studies, using SCID provides a better chance to avoid cancer cell rejection. In this review, we describe the main directions of using ZF in research, explain why and how zebrafish can be used as a model, what kind of limitations will be met and how to overcome them. We collected recent achievements in this field, indicating promising perspectives for the future.

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Section: Aim Of the Studies—what Is The Point?supporting

confidence: 68%

Section: Disease Induction: How To Create a Fish Modelmentioning

confidence: 99%

Section: Aim Of the Studies—what Is The Point?mentioning

confidence: 99%

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One Host-Multiple Applications: Zebrafish (Danio rerio) as Promising Model for Studying Human Cancers and Pathogenic Diseases

Dudziak

Nowak

Sozoniuk

2022

IJMS

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“…Furthermore, GSEA analysis revealed that these DEGs might affect base excision repair, the cell cycle, DNA replication, mismatch repair, and the p53 signaling pathway. The most activated p53 signaling pathway, which has been linked to oncogenic effects 38 , promotes tumor growth in NSCLC and pancreatic ductal adenocarcinoma (PDAC) 39,40 . However, these DEGs' specific functions and molecular mechanisms need to be investigated further.…”

Section: Discussionmentioning

confidence: 99%

Identidication of novel biomarkers in non-small cell lung cancer using machine learning

Wang

2022

Sci Rep

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Lung cancer is one of the leading causes of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) accounts for a large proportion of lung cancer cases, with few diagnostic and therapeutic targets currently available for NSCLC. This study aimed to identify specific biomarkers for NSCLC. We obtained three gene-expression profiles from the Gene Expression Omnibus database (GSE18842, GSE21933, and GSE32863) and screened for differentially expressed genes (DEGs) between NSCLC and normal lung tissue. Enrichment analyses were performed using Gene Ontology, Disease Ontology, and the Kyoto Encyclopedia of Genes and Genomes. Machine learning methods were used to identify the optimal diagnostic biomarkers for NSCLC using least absolute shrinkage and selection operator logistic regression, and support vector machine recursive feature elimination. CIBERSORT was used to assess immune cell infiltration in NSCLC and the correlation between biomarkers and immune cells. Finally, using western blot, small interfering RNA, Cholecystokinin-8, and transwell assays, the biological functions of biomarkers with high predictive value were validated. A total of 371 DEGs (165 up-regulated genes and 206 down-regulated genes) were identified, and enrichment analysis revealed that these DEGs might be linked to the development and progression of NSCLC. ABCA8, ADAMTS8, ASPA, CEP55, FHL1, PYCR1, RAMP3, and TPX2 genes were identified as novel diagnostic biomarkers for NSCLC. Monocytes were the most visible activated immune cells in NSCLC. The knockdown of the TPX2 gene, a biomarker with a high predictive value, inhibited A549 cell proliferation and migration. This study identified eight potential diagnostic biomarkers for NSCLC. Further, the TPX2 gene may be a therapeutic target for NSCLC.

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“…According to Wu et al ( 53 ), activated p38 MAPK is a pro-apoptotic signal for curcumin-induced mortality of chemoresistant human lung cancer cells A549. Theabrownin, a component of green tea, suppresses human NSCLC in a xenograft model via activating the MAPK/JNK signaling pathway, according to Xiao et al ( 54 ). Liu et al ( 55 ) found that elevated KLHL17 in NSCLC promotes tumor growth and migration via activating the Ras/MAPK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

et al. 2022

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KRAS is a biomarker for non-small cell lung cancer-targeted therapy, but there is currently no effective KRAS-targeting medication. Realgar is an impelling anticancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC 50 of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non-KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 µg/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe 2+ , reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer-1. Realgar decreased phosphorylated p-Raf, p-ERK1/2 and increased p-p38 and p-JNK, whereas only p-Raf was abolished by Fer-1. Raf inhibitor Sorafenib accelerated the realgar-induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti-KRAS mutant lung cancer.

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Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway

Cited by 20 publications

References 59 publications

One Host-Multiple Applications: Zebrafish (Danio rerio) as Promising Model for Studying Human Cancers and Pathogenic Diseases

One Host-Multiple Applications: Zebrafish (Danio rerio) as Promising Model for Studying Human Cancers and Pathogenic Diseases

Identidication of novel biomarkers in non-small cell lung cancer using machine learning

Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

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