Muscone derivative ZM-32 inhibits breast tumor angiogenesis by suppressing HuR-mediated VEGF and MMP9 expression

Yang, Liuqing; Yu, Shao-Peng; Yang, Yantao; Zhao, Ying; Wang, Feiyun; Chen, Yao; Li, Qinghua; Tian, Ping; Zhu, Yuying; Zhang, Jiange; Lin, Guo‐Qiang

doi:10.1016/j.biopha.2021.111265

Cited by 20 publications

(12 citation statements)

References 37 publications

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“…Ke et al reported that the extracts of foeniculum vulgare seed could promote lung cancer cells apoptosis by suppressing the Bcl-2 expression [ 4 ]. ZM-32, one of muscone derivative, had been proved to exert an inhibitory function in breast tumor angiogenesis through effectively blocking the interaction between HuR and VEGF [ 5 ]. A typical flavonoid compound, baicalein, extracted from the root of Scutellaria baicalensis, inhibited lung cancer cell proliferation via inducing degradation of MAP4K3.…”

Section: Introductionmentioning

confidence: 99%

[6]-Paradol suppresses proliferation and metastases of pancreatic cancer by decreasing EGFR and inactivating PI3K/AKT signaling

et al. 2021

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Background The underlying mechanism behind the tumorigenesis and progression of pancreatic cancer is not clear, and treatment failure is generally caused by early metastasis, recurrence, drug resistance and vascular invasion. Exploring novel therapeutic regimens is necessary to overcome drug resistance and improve patients outcomes. Methods Functional assays were performed to investigate the role of [6]-Paradol (6-P) in proliferation and metastasis of pancreatic cancer in vitro and in vivo. The interaction between EGFR and 6-P was tested by KEGG enrichment analysis and molecular docking analysis. qRT-PCR was performed to detect the mRNA expression of EGFR in 6-P treated groups. Involvement of the PI3K/AKT pathway was measured by western blotting. Results 6-P significantly suppressed pancreatic cancer cell proliferation and metastasis. KEGG enrichment analysis and molecular docking analysis suggested that there existed certain interaction between EGFR and 6-P. In addition, 6-P obviously decreased EGFR protein expression level but did not change the mRNA expression level of EGFR. 6-P could induce degradation of EGFR through decreasing the protein stability of EGFR and enhancing the ubiquitin-mediated proteasome-dependent degradation, 6-P-mediated EGFR degradation led to inactivation of PI3K/AKT signaling pathway. However, ectopic expression of EGFR protein resulted in resistance to 6-P-mediated inactivity of PI3K/AKT signaling and inhibition of malignant phenotype of pancreatic cancer. Inversely, erlotinib could enhance the 6-P-mediated anticancer activity. Conclusion Our data indicated that 6-P/EGFR/PI3K/AKT signaling axis might become one of the potential therapies for the treatment of pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

[6]-Paradol suppresses proliferation and metastases of pancreatic cancer by decreasing EGFR and inactivating PI3K/AKT signaling

et al. 2021

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“…A total of 29 compounds were found in the BATMAN-TCM analysis platform, including muscone, muscopyridine, estradiol, androgen, and morin (37). In a rat model of cerebral ischemia, muscone and medicines such as ligustilide and hydroxysafflor yellow A could up-regulate the expression of ZO-1, occludin, and claudin-5 and downregulate aquaporin-4 (AQP-4) (38). On the other hand, the results of musk and other drugs in an animal model of cerebral hemorrhage showed that treatment with TCM and acupuncture could improve neurological dysfunction (39).…”

Section: Discussionmentioning

confidence: 99%

Network pharmacological analysis of active components of Tongqiao Huoxue Decoction in the treatment of intracerebral hemorrhage

Wu¹,

Li²,

Liang³

et al. 2022

Ann Transl Med

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Background: Intracerebral hemorrhage (ICH) is a type of stroke which results in a high disability and mortality rate and has a poor prognosis. Tongqiao Huoxue Decoction (TQHXD) is a classical Chinese prescription. Clinical practice has proven that TQHXD can promote blood circulation and can effectively treat ICH and its sequelae. However, the current mechanism is still unclear.Methods: The chemical components and target genes of TQHXD were collected from the Traditional Chinese medicine (TCM) Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine analysis platforms, and the gene expression data of ICH tissues were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to obtain differentially co-expressed gene pairs and build a drugtarget-disease network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained target genes and shared genes. Finally, molecular docking was carried out to further clarify the utility of TQHXD for the treatment of ICH.Results: A total of 304 differentially expressed genes in ICH, 42 TQHXD active ingredients, and 279 predicted targets of its active compounds were obtained. Bioinformatics analysis showed that they were involved in angiogenesis, the regulation of wound healing, and other biological processes. Furthermore, their participation in fluid shear stress and the atherosclerosis signaling pathway indicated their close association with the pathological processes of ICH. Finally, molecular docking was carried out to further confirm the tightly binding structural sites of the effective components of TQHXD and key proteins.Conclusions: In summary, the results of this study suggest that the mechanism of action of TQHXD in the treatment of ICH involves multiple targets and signaling pathways related to its occurrence and development. This study not only provides a new theoretical basis for the treatment of ICH with traditional Chinese medicine, but also provides new ideas for the research and development of drugs for the treatment of ICH.

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“…The moscatilin derivative 8Ae performed more effective angiogenesis inhibition in zebrafish assay (0.62–1.25 μM) than positive drug SU5416 ( Guan et al, 2019 ). Muscone derivative ZM-32 attenuated the stabilizing effect of RNA-binding protein HuR toward Vegf-a and Mmp9 mRNA, thus resulting in downregulation of VEGF-A and MMP-9 expression in HUVECs and breast cancer MDA-MB-231 cells ( Yang et al, 2021a ).…”

Section: The Analogs From Medical Chemistrymentioning

confidence: 99%

Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology

et al. 2022

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Tumor angiogenesis is one of the most important processes of cancer deterioration via nurturing an immunosuppressive tumor environment (TME). Targeting tumor angiogenesis has been widely accepted as a cancer intervention approach, which is also synergistically associated with immune therapy. However, drug resistance is the biggest challenge of anti-angiogenesis therapy, which affects the outcomes of anti-angiogeneic agents, and even combined with immunotherapy. Here, emerging targets and representative candidate molecules from ethnopharmacology (including traditional Chinese medicine, TCM) have been focused, and they have been proved to regulate tumor angiogenesis. Further investigations on derivatives and delivery systems of these molecules will provide a comprehensive landscape in preclinical studies. More importantly, the molecule library of ethnopharmacology meets the viability for targeting angiogenesis and TME simultaneously, which is attributed to the pleiotropy of pro-angiogenic factors (such as VEGF) toward cancer cells, endothelial cells, and immune cells. We primarily shed light on the potentiality of ethnopharmacology against tumor angiogenesis, particularly TCM. More research studies concerning the crosstalk between angiogenesis and TME remodeling from the perspective of botanical medicine are awaited.

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Muscone derivative ZM-32 inhibits breast tumor angiogenesis by suppressing HuR-mediated VEGF and MMP9 expression

Cited by 20 publications

References 37 publications

[6]-Paradol suppresses proliferation and metastases of pancreatic cancer by decreasing EGFR and inactivating PI3K/AKT signaling

[6]-Paradol suppresses proliferation and metastases of pancreatic cancer by decreasing EGFR and inactivating PI3K/AKT signaling

Network pharmacological analysis of active components of Tongqiao Huoxue Decoction in the treatment of intracerebral hemorrhage

Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology

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