&lt;p&gt;Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway&lt;/p&gt;

Yang, Shen Hsi; Chen, Jin; Tan, Tao; Wang, Nan; Huang, Yanran; Wang, Yuping; Yuan, Xiaohui; Zhang, Ping; Luo, Jinyong; Luο, Xingguang

doi:10.2147/cmar.s238093

Cited by 16 publications

(16 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evodiamine is a novel alkaloid, which was isolated from the fruit of Tetradium [32], and it has been considered an effective Chinese medicine for the treatment of gastropathy, hypertension, and eczema [33]. Several studies reported that evodiamine has various biological effects, including anti-nociceptive, anti-bacterial, antiobesity and anti-cancer activities [34][35][36]. However, to date, the effect of evodiamine on the PD-1/PD-L1 axis remains underexplored.…”

Section: Introductionmentioning

confidence: 99%

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Jiang

Huang

Xie

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC). Methods Cell viability was measured by MTT assays. Apoptosis, cell cycle and surface PD-L1 expression on NSCLC cells were analyzed by flow cytometry. The expression of MUC1-C and PD-L1 mRNA was measured by real time RT-PCR methods. Protein expression was examined in evodiamine-treated NSCLC cells using immunoblotting or immunofluorescence assays. The effects of evodiamine treatment on NSCLC sensitivity towards T cells were investigated using human peripheral blood mononuclear cells and Jurkat, apoptosis and IL-2 secretion assays. Female H1975 xenograft nude mice were used to assess the effect of evodiamine on tumorigenesis in vivo. Lewis lung carcinoma model was used to investigate the therapeutic effects of combination evodiamine and anti-PD-1 treatment. Results We showed that evodiamine significantly inhibited growth, induced apoptosis and cell cycle arrest at G2 phase of NSCLC cells. Evodiamine suppressed IFN-γ-induced PD-L1 expression in H1975 and H1650. MUC1-C mRNA and protein expression were decreased by evodiamine in NSCLC cells as well. Evodiamine could downregulate the PD-L1 expression and diminish the apoptosis of T cells. It inhibited MUC1-C expression and potentiated CD8+ T cell effector function. Meanwhile, evodiamine showed good anti-tumor activity in H1975 tumor xenograft, which reduced tumor size. Evodiamine exhibited anti-tumor activity by elevation of CD8+ T cells in vivo in Lewis lung carcinoma model. Combination evodiamine and anti-PD-1 mAb treatment enhanced tumor growth control and survival of mice. Conclusions Evodiamine can suppress NSCLC by elevating of CD8+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma.

show abstract

Section: Introductionmentioning

confidence: 99%

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Jiang

Huang

Xie

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Therefore, Berberine should be combined with Evodiamine to achieve the synergistic effect and improve the antiproliferative and anti-migratory properties against colon cancer cell malignant transformation by modulating TGF-β1 expression. The combination regulates differentiation of colon epithelial cells by downregulating miR-42 and suppressing activity of TGF-β/Smad signaling 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Berberine and Evodiamine Synergically Exert Anti-colorectal Cancer Effeccts via P38/MAPK/MAPKAPK2/HSP27 Signaling Pathway

Chen

Jiang

Yang

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective: Combinatorial natural products have high application potential for treatment of complex diseases owing to their synergistic effects and multi-targeting effect. However, studies have not explored the therapeutic effect and the synergetic mechanisms of action combinations of natural products. The present study aimed sought to evaluate the synergistic antitumor effects of a combination of Berberine and Evodiamine, and explore the drug effect on proliferation, migration, invasion of HCT116 and RKO human colorectal cancer cells. Results: The effect of berberine and evodiamine at a specific paired dose (BER30μM, EVO 0.8μM) was explored. A combination of berberine and evodiamine had no effect on activity and proliferation of HCT116 and RKO cells. The combination regulates the cell cycle of HCT116 and RKO cells at different cell phases. Berberine mainly blocked the cell cycle at G0/G1 phase, whereas evodiamine induced cell cycle arrest at G2/M phase. The results showed that the combined effect of berberine and evodiamine does not offset each other, but plays a synergistic role in regulation of colon cancer cell cycle. Western blot analysis showed that the combination of berberine and evodiamine regulated cell cycle by downregulating expression of cdc25c and upregulating expression of p21. The combination significantly inhibited cell migration and invasion by regulating EMT related proteins, upregulating expression of E-cadherin and downregulating expression of N-cadherin. The combination of berberine and evodiamine significantly inhibited phosphorylation of P38 MAPK in HCT116 and RKO cells, and further inhibited phosphorylation of the downstream MAPKAPK2 and HSP27, thus playing a synergistic anti-colon cancer role.Conclusion: Berberine and Evodiamine exhibit synergistic antitumor effects by suppressing cell proliferation, inducing cell cycle arrest and inhibiting EMT by modulating P38MAPK /MAPKAPK2/HSP27 pathway.Significance of the study: To illustrate the potential mechanism of formula-based combination of natural products, and explore the potential applications of the combination and possible antitumor therapeutic targets.

show abstract

“…Moreover, EVO suppresses cancer growing by eliminating stemness and inhibiting invasion and migration (7,31). This is mainly due to the downregulation of epithelial-mesenchymal transition (EMT) (32)(33)(34). For instance, EVO elevated epithelial marker E-cadherin and reduced the expression of mesenchymal markers N-cadherin and vimentin (33), as well as matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) protein levels (32).…”

Section: Discussionmentioning

confidence: 99%

“…This is mainly due to the downregulation of epithelial-mesenchymal transition (EMT) (32)(33)(34). For instance, EVO elevated epithelial marker E-cadherin and reduced the expression of mesenchymal markers N-cadherin and vimentin (33), as well as matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) protein levels (32). Many in vitro and in vivo studies had reported beneficial effects of EVO against tumor, and as far as we know, this is the first meta-analysis that assessed the anticancer effect of EVO in preclinical experiments.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effects of Evodiamine in Mice Model Experiments: A Systematic Review and Meta-Analysis

et al. 2021

View full text Add to dashboard Cite

BackgroundEvodiamine (EVO), an alkaloid extracted from the traditional Chinese medicine Euodia rutaecarpa, plays an important role in the treatment of cancer. This study was performed to clarify the effects of evodiamine in mice tumor model studies.MethodsElectronic databases and search engines involved China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, and ClinicalTrials.gov databases, which were searched for literature related to the antitumor effects of evodiamine in animal tumor models (all until 1 October 2021). The evodiamine effects on the tumor volume and tumor weight were compared between the treatment and control groups using the standardized mean difference (SMD).ResultsEvodiamine significantly inhibited tumor growth in mice, as was assessed with tumor volume [13 studies, n=267; 138 for EVO and 129 for control; standard mean difference (SMD)= -5.99; 95% (CI): -8.89 to -3.10; I2 = 97.69%, p ≤ 0.00], tumor weight [6 studies, n=89; 49 for EVO and 40 for control; standard mean difference (SMD)= -3.51; 95% (CI): -5.13 to -3.90; I2 = 83.02%, p ≤ 0.00].ConclusionEVO significantly suppresses tumor growth in mice models, which would be beneficial for clinical transformation. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether EVO can be used in the adjuvant treatment of clinical tumor patients.

show abstract

<p>Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway</p>

Cited by 16 publications

References 52 publications

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Berberine and Evodiamine Synergically Exert Anti-colorectal Cancer Effeccts via P38/MAPK/MAPKAPK2/HSP27 Signaling Pathway

Antitumor Effects of Evodiamine in Mice Model Experiments: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About