Andrographolide Inhibits Angiogenesis by Inhibiting the Mir-21-5p/TIMP3 Signaling Pathway

Dai, Jianwei; Lin, Yuwan; Duan, Youfa; Li, Zixuan; Zhou, Da‐Lei; Chen, Wensheng; Wang, Lijing; Zhang, Qianqian

doi:10.7150/ijbs.19194

Cited by 34 publications

(29 citation statements)

References 37 publications

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“…miR-21-5p is considered to be an important tumour-related miRNA. It was found that miR-21-5p was associated with the growth and metastasis of multiple solid tumours 18. In a study investigating brain glioblastoma, miR-21-5p has been highly expressed 19.…”

Section: Discussionmentioning

confidence: 99%

Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis

et al. 2019

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ObjectiveChanges in microRNAs (miRNAs) in the cerebrospinal fluid (CSF) are associated with different neurological diseases. Since alternations of miRNAs in neurosyphilis are insufficiently investigated, we analysed miRNAs in the CSF of patients suffering from neurosyphilis.MethodsExosomes were isolated from serum and CSF. Levels of 44 miRNAs were determined using quantitative real-time PCR-based miRNA array.ResultsIn patients with neurosyphilis (NSP), miR-590-5p, miR-570-3p and miR-570-5p were upregulated in the CSF and serum, when compared with patients with syphilis without neurosyphilis (SP). miR-590-5p and miR-570-3p were significantly upregulated (p<0.001). The expression of miR-21-5p was upregulated only in the CSF of NSP. Significant downregulation was observed for miR-93-3p in the CSF and serum of NSP. No statistical difference was found in the expression of miR-7-5p, miR-1307-5p, miR-203a-3p, miR-16, miR-23b-3p and miR-27b-5p in the CSF and serum of NSP and SP.ConclusionFor the first time, regulation profiles in miRNA in the CSF and serum were analysed in NSP. We found significant differences in upregulation and downregulation. Therefore, miRNAs may be potential biomarkers for the presence of neurosyphilis.

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Section: Discussionmentioning

confidence: 99%

Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis

et al. 2019

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“…TIMP3 is directly targeted by miR-21-5p. Andrographolide repressed miR-21-5p and stimulated the expression of TIMP3 [64]. Therefore, it seems clear that andrographolide interferes with angiogenesis mainly through the inhibition of miR-21-5p and upregulation of TIMP3.…”

Section: Regulation Of Micrornasmentioning

confidence: 95%

“…The inhibition of oncogenic miRNAs has been studied contextually in different cancers. MDA-MB-231 cells were cultured on chick embryo chorioallantoic membrane to unveil how andrographolide exerted anti-angiogenic effects [64]. Andrographolide attenuated neovascularization in the tumor tissues in a dose-dependent manner.…”

Section: Regulation Of Micrornasmentioning

confidence: 99%

The Prowess of Andrographolide as a Natural Weapon in the War against Cancer

Farooqı

Attar

Sabitaliyevich

et al. 2020

Cancers

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There has been a paradigm shift in our understanding about the multifaceted nature of cancer and a wealth of information has revealed that single-target drugs are not good enough to provide satisfactory clinical outcomes and therapeutic effects for complex diseases which involve multiple factors. Therefore, there has been a reignition to search for natural products having premium pharmacological activities aim to efficiently target multiple deregulated cellular signaling pathways. Andrographolide, a diterpene lactone from Andrographis paniculata was brought into to the limelight because of its ability to inhibit cancer cell proliferation and induce apoptosis. Here we review andrographolide on cellular pathways regulation including Wnt/β-catenin, mTOR, VEGF-mediated intracellular signaling, as well as TRAIL-mediated apoptosis to inhibit cancer development.

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“…3D, P < 0.05 respectively). We also monitored the anti-angiogenic signaling property of AGP since AGP has been reported to limit angiogenesis signaling in some models [30,31]. Levels of VEGF 165 and FOXM1 in mice harvested 4 h PO AGP treatment showed decreased expression (Fig.…”

Section: Agp Induces Er Stress Tumor Suppressor Gene Expression Andmentioning

confidence: 99%

Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

Blanchard

Lapidus

Banerjee

et al. 2018

Cell Physiol Biochem

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Background/Aims: Silencing of tumor suppressor genes (TSGs) and promotion of angiogenesis are associated with tumor development and metastasis. However, little is known if angiogenic molecules directly control TSGs and vice versa. Methods: A regulatory link between angiogenesis and down regulation of TSGs was evaluated using an anti-cancer agent, andrographolide (AGP) in cancer cells, mouse xenograft tissues and patient derived organoids through gene/protein expression, gene silencing, and immunohistochemical analyses. Results: AGP treatment demonstrated significant expression of RASSF1A and PTEN TSGs in colon cancer and other cancer cells, mouse tissues and organoids. Depletion of RASSF1A with siRNA limited cyclin D1 and BAX expression. SiRNA depletion of PTEN, upstream regulator of RASSF1A resulted in a 50% reduction in RASSF1A expression. Histopathological analysis of the AGP treated tumor sections showed significant reduction in vessel size, microvascular density and tumor mitotic index suggesting suppression of angiogenesis. This was corroborated by protein analysis demonstrating significant reductions in angiogenesis signaling pathway molecules VEGF₁₆₅, FOXM1, and pAkt, but significant elevation of the endogenous angiogenesis inhibitor Tsp-2. Treatment of cells with exogenous VEGF prevented the suppression of angiogenesis signaling by AGP, resulting in sustained expression of pAkt, an upstream down-regulator of RASSF1A. RASSF1A expression remained low in VEGF treated cells despite the addition of AGP. Conclusion: Our results demonstrate for the first time that AGP induces RASSF1A expression in colon cancer cells and is dependent on angiogenesis signaling events. Therefore, our research may facilitate novel therapeutic options for advanced colon cancer therapy.

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Andrographolide Inhibits Angiogenesis by Inhibiting the Mir-21-5p/TIMP3 Signaling Pathway

Cited by 34 publications

References 37 publications

Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis

Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis

The Prowess of Andrographolide as a Natural Weapon in the War against Cancer

Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

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