Baicalein is a novel TLR4‐targeting therapeutics agent that inhibits TLR4/HIF‐1α/VEGF signaling pathway in colorectal cancer

Chen, Minting; Zhong, Keying; Tan, Jincheng; Meng, Mingjing; Liu, Chok Mei; Chen, Baisen; Huang, Chunhua; Wong, Hoi Leong Xavier; Bian, Zhaoxiang; Su, Tao; Kwan, Hiu Yee

doi:10.1002/ctm2.564

Cited by 38 publications

(29 citation statements)

References 10 publications

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“…Interestingly, recent studies demonstrate that baicalein, a bioactive flavonoid, directly binds to toll-like receptor 4 (TLR4), hence reducing VEGF expression, which leads to the inhibition of tumor growth and angiogenesis and reduces the cancer’s metastatic potential [ 56 , 57 ].…”

Section: Possible Utilities Of Vegf Family Members In Colorectal Cancermentioning

confidence: 99%

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

Dakowicz

Zajkowska

Mroczko

2022

IJMS

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Colorectal cancer (CRC) is the second most common cause of cancer death in the world. Both modifiable and nonmodifiable risk factors play a significant role in the pathogenesis of this tumor. The diagnosis is usually made late due to limitations of screening tests; therefore, the scientists are looking for new diagnostic tools such as gene or miRNA expression or different proteins’ concentrations, e.g., vascular endothelial growth factor (VEGF) family members. The VEGF family (VEGF-A, VEGF-B, VEGF-C, VEGF-D and PlGF) plays a key role in the processes of blood vessel formation in embryonic development as well as in pathological angiogenesis and lymphangiogenesis, which allow the tumor to grow exponentially. Blockage of VEGF-related pathways seems to be a valid therapeutic target. It was suggested in recent studies, that besides already used drugs, e.g., bevacizumab, there are other agents with potential usefulness in anticancer activity such as miRNAs, TMEA, granzyme K, baicalein and arginine. Moreover, VEGF proteins were assessed to induce the expression of anti-apoptotic proteins such as BCL-2 and BAX. Therefore, investigations concerning the usefulness of VEGF family members, not only in the development but also in the therapy of CRC, in order to fully elucidate their role in carcinogenesis, are extremely important.

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Section: Possible Utilities Of Vegf Family Members In Colorectal Cancermentioning

confidence: 99%

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

Dakowicz

Zajkowska

Mroczko

2022

IJMS

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“…Then, a series of downstream signals are activated and finally upregulate the expression of pro-inflammatory cytokines ( Kumar et al, 2011 ; Moghimpour Bijani et al, 2012 ). It was reported that baicalein, a main component in SR, could directly bind to TLR4 to interrupt the formation of the complex (LPS-MD2-TLR4) ( Chen et al, 2021 ). Luteolin, 3′,4′,5,7-tetrahydroxyflavone, was found to significantly improve the survival rate of endotoxemia mice by combining in an interface of LPS and MD-2 to prevent the formation of the complex ( Yan et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

A Candidate Drug Screen Strategy: The Discovery of Oroxylin A in Scutellariae Radix Against Sepsis via the Correlation Analysis Between Plant Metabolomics and Pharmacodynamics

et al. 2022

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Sepsis is an acute systemic infectious disease with high mortality, which urgently needs more effective treatment. Scutellariae radix (SR), a commonly used traditional Chinese medicine (TCM) for clearing heat and detoxification, contains rich natural products possessing anti-inflammatory activity. In previous studies, it was found that the anti-inflammatory activities of SR extracts from different ecological conditions varied wildly. Based on this, in the present study, a screening strategy of antisepsis active components from SR based on correlation analysis between plant metabolomics and pharmacodynamics was established, and the mechanism was explored. First of all, a mass spectrum database of SR (above 240 components) was established to lay the foundation for the identification of plant metabolomics by liquid chromatography tandem mass spectrometry (LC–MS/MS). Through the correlation analysis between plant metabolomics and anti-inflammatory activity of SR from different ecology regions, 10 potential components with high correlation coefficients were preliminarily screened out. After the evaluation of anti-inflammatory activity and toxicity at the cellular level, the pharmacodynamic evaluation in vivo found that oroxylin A had the potentiality of antisepsis both in LPS- and CLP-induced endotoxemia mice. Network pharmacology and Western blot (WB) results indicated that oroxylin A significantly inhibited the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway, which was further confirmed by secreted embryonic alkaline phosphatase (SEAP) assay. Moreover, the molecular docking analysis indicated that oroxylin A might competitively inhibit LPS binding to myeloid differentiation 2 (MD-2) to block the activation of TLR4. The study provided a feasible research strategy for the screening and discovery of antisepsis candidate drugs from TCM.

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“…Toll-like receptor 4 (TLR4) could induce the PI3K/AKT signaling and play a central role in the progression of CRC [ 43 ]. Moreover, baicalein directly bound to TLR4 to inhibit TLR4/HIF-1α/VEGF signaling pathway and angiogenesis in CRC [ 44 ]. Ginkgetin and resveratrol could inhibit VEGF-mediated angiogenesis during tumorigenesis ( Figure 1 ).…”

Section: Vegf Signaling Pathway In Crcmentioning

confidence: 99%

Classical Angiogenic Signaling Pathways and Novel Anti-Angiogenic Strategies for Colorectal Cancer

Cao

Wang²,

Lu³

et al. 2022

CIMB

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Although productive progress has been made in colorectal cancer (CRC) researchs, CRC is the second most frequent type of malignancy and the major cause of cancer-related death among gastrointestinal cancers. As angiogenesis constitutes an important point in the control of CRC progression and metastasis, understanding the key signaling pathways that regulate CRC angiogenesis is critical in elucidating ways to inhibit CRC. Herein, we comprehensively summarized the angiogenesis-related pathways of CRC, including vascular endothelial growth factor (VEGF), nuclear factor-kappa B (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless and int-1 (Wnt), and Notch signaling pathways. We divided the factors influencing the specific pathway into promoters and inhibitors. Among these, some drugs or natural compounds that have antiangiogenic effects were emphasized. Furthermore, the interactions of these pathways in angiogenesis were discussed. The current review provides a comprehensive overview of the key signaling pathways that are involved in the angiogenesis of CRC and contributes to the new anti-angiogenic strategies for CRC.

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Baicalein is a novel TLR4‐targeting therapeutics agent that inhibits TLR4/HIF‐1α/VEGF signaling pathway in colorectal cancer

Cited by 38 publications

References 10 publications

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

A Candidate Drug Screen Strategy: The Discovery of Oroxylin A in Scutellariae Radix Against Sepsis via the Correlation Analysis Between Plant Metabolomics and Pharmacodynamics

Classical Angiogenic Signaling Pathways and Novel Anti-Angiogenic Strategies for Colorectal Cancer

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