Dataset Information

Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation.

ABSTRACT: Eupalinolide J (EJ) is an active component from Eupatorium lindleyanum DC. (EL), which was reported to have good antitumor activity via STAT3 and Akt signaling pathways. In this study, we identified Eupalinolide J (EJ) as a potential anti-cancer metastatic agent by target prediction and molecular docking technique screening. Follow-up experiments demonstrated that EJ exhibited a good inhibitory effect on cancer cell metastasis both in vitro and in vivo, and could effectively reduce the expression of STAT3, MMP-2, and MMP-9 proteins in cells, while the knockdown of STAT3 could weaken the inhibitory effect of EJ on cancer cell metastasis. Further molecular biology experiments revealed that EJ promoted STAT3 ubiquitin-dependent degradation, and thus, downregulated the expression of the metastasis-related genes MMP-2 and MMP-9. In conclusion, our study revealed that EJ, a sesquiterpene lactone from EL, could act as a STAT3 degradation agent to inhibit cancer cell metastasis and is expected to be applied in cancer therapy.

SUBMITTER: Hu H

PROVIDER: S-EPMC10096386 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation.

Hu Hongtao H Bai Haoyang H Huang Lili L Yang Bo B Zhao Huajun H

Molecules (Basel, Switzerland) 20230331 7

Eupalinolide J (EJ) is an active component from <i>Eupatorium lindleyanum</i> DC. (EL), which was reported to have good antitumor activity via STAT3 and Akt signaling pathways. In this study, we identified Eupalinolide J (EJ) as a potential anti-cancer metastatic agent by target prediction and molecular docking technique screening. Follow-up experiments demonstrated that EJ exhibited a good inhibitory effect on cancer cell metastasis both in vitro and in vivo, and could effectively reduce the ex ...[more]

PMID: 37049904

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Project description:BackgroundGastric cancer (GC) is a common malignancy with a poor prognosis. Tripartite motif-containing 50 (TRIM50) belongs to the TRIM family and is reported to be related to numerous cancers. This study aimed to investigate the function of TRIM50 in GC.MethodsThree microarray datasets (GSE13911, GSE79973, and GSE19826) containing GC and adjacent nontumor tissues were used for bioinformatics analysis to screen GC-related genes and assess the associations between GC development and TRIM50 expression. Then, TRIM50 expression in GC cells was detected at mRNA and protein levels. After TRIM50 was knockdown or overexpressed, the effect of TRIM50 on the proliferation and metastasis of GC cells was analyzed using Cell Counting Kit-8 (CCK-8), flow cytometry, scratch, and Transwell assays. The interaction between TRIM50 and β-catenin was analyzed. The expression of cell cycle-, migration-, invasion-, and Wnt/β-catenin signaling pathway-related proteins was detected by Western blot. Furthermore, we measured the role of TRIM50 overexpression on tumor growth as well as the Wnt/β-catenin signaling pathway in vivo. In addition, XAV939 (a WNT/β-catenin signaling pathway inhibitor) was used to clarify the mechanism of TRIM50 on GC.ResultsBioinformatics revealed that TRIM50 expression was decreased in GC samples and associated with GC development. In vitro study revealed that TRIM50 overexpression impeded the GC cell proliferation and metastasis, while TRIM50 knockdown presented the opposite results. In addition, TRIM50 interacted with β-catenin to induce the degradation of β-catenin. In in vivo assay, TRIM50 overexpression inhibited tumor growth and blocked the Wnt/β-catenin signaling pathway. In addition, TRIM50 knockdown-promoted cell proliferation and metastasis in GC cells were inverted by XAV939.ConclusionTRIM50 overexpression may inhibit cell proliferation and metastasis in GC via β-catenin degradation, indicating that TRIM50 could be a target for the treatment of GC.

Dataset Information

Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation.

Publications

Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation.

Similar Datasets

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