Sinensetin suppresses angiogenesis in liver cancer by targeting the VEGF/VEGFR2/AKT signaling pathway

Li, Xiaο; Li, Yan; Wang, Yuan; Liu, Fuhong; Liu, Yanjun; Liang, Jiangjiu; Zhan, Renya; Wu, Yue; Ren, He; Zhang, Xiuyuan; Liu, Ju

doi:10.3892/etm.2022.11287

Cited by 9 publications

(4 citation statements)

References 53 publications

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“…Otherwise, SNS would target p53-mediated AMPK/mTOR signaling to trigger autophagy and apoptosis of Hepatocellular Carcinoma Cells . SNS also inhibited VEGF/VEGFR2/AKT signaling to impaired angiogenesis in liver cancer . Thus, we and others showed that SNS possesses a protective role in lung and liver diseases.…”

Section: Discussionmentioning

confidence: 89%

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Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

Lin,

Deng,

Gong

et al. 2023

ACS Omega

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Macrophage-mediated inflammation plays essential roles in multiple-organ injury. Sinensetin (SNS) at least exhibits anti-inflammation, antioxidant, and antitumor properties. However, the underlying mechanism of SNS-targeted macrophage-mediated inflammation remains elusive. In the present study, our results showed that SNS suppressed lipopolysaccharide (LPS)-induced inflammation to ameliorate lung and liver injuries. Mechanistically, SNS significantly inhibited M1-type macrophage polarization and its NLRP3 inflammasome formation to significantly decrease tumor necrosis factor α (TNFα) and IL-6 expression, while increasing IL-10 expression. Moreover, SNS interacted and activated SIRT1 to promote NRF2 and its target gene SOD2 transcription, which subsequently decreased LPS-induced inflammation. SIRT1 knockdown impaired the effects of SNS on the inhibition of macrophage polarization, NLRP3 inflammasome formation, and NRF2/SOD2 signaling. Taken together, our results showed that SNS is a potential and promising natural active ingredient to ameliorate inflammatory injury via activating SIRT1/NRF2/SOD2 signaling.

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Section: Discussionmentioning

confidence: 89%

“…27 SNS also inhibited VEGF/VEGFR2/AKT signaling to impaired angiogenesis in liver cancer. 28 Thus, we and others showed that SNS possesses a protective role in lung and liver diseases. Accumulating evidence highlighted that macrophage was involved in and initiated the inflammatory injury.…”

Section: Discussionmentioning

confidence: 89%

Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

Lin,

Deng,

Gong

et al. 2023

ACS Omega

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“…Researchers have found that NBIF induces mitochondrial outer membrane protein Tom20 alteration through ROS both in vivo and in vitro, thereby enhancing Bax recruitment to mitochondria and activating the calpain I-GSDME pathway in liver cancer cells to induce pyroptosis. Sinensetin (SIN), a polymethoxylated flavone found in citrus fruits, inhibits angiogenesis in liver cancer by targeting the VEGF/VEGFR2/AKT signaling pathway in a murine xenograft tumor model [ 51 ]. Studies indicate that extramedullary hematopoiesis (EMH) is a crucial mechanism for myeloid-derived suppressor cells (MDSCs) accumulation in tumor tissues, contributing to disease progression.…”

Section: Nps With Therapeutic Activity For Liver Cancermentioning

confidence: 99%

“…The results revealed decreased expression of MMP2, MMP9, and VEGF in the rat liver, accompanied by increased levels of TIMP3 and miR-1-3p expression, suggesting that the anti-angiogenic effect of TQ in HCC is mediated through miR-1-3p regulation [ 116 ]. Natural polysaccharides like Asparagus polysaccharide, flavonoids like sinensetin, and polyphenols like tannins have also been found to exert anti-hepatocellular carcinoma effects by inhibiting tumor angiogenesis [ 51 , 106 , 128 ].…”

Section: The Main Action Pathway and Potential Mechanism Of Natural C...mentioning

confidence: 99%

Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms

Guo,

Yan,

Duan

et al. 2024

Nutrients

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Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.

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Sinensetin inhibits the movement ability and tumor immune microenvironment of non‐small cell lung cancer through the inactivation of AKT/β‐catenin axis

Shi,

Shen,

Liu

et al. 2024

J Biochem & Molecular Tox

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Although current treatment strategies have improved clinical outcomes of non‐small cell lung cancer (NSCLC) patients, side effect and prognosis remain a hindrance. Thus, safer and more effective therapeutical drugs are needed for NSCLC. Sinensetin (Sin) is a flavonoid from citrus fruits, which exhibits antitumor effect on diverse cancers. However, the effect and mechanism of Sin on NSCLC remain unknown. In this study, NSCLC cell lines, and tumor‐bearing mice were treated with Sin. The effect and mechanism of Sin were addressed using cell counting kit‐8, transwell, enzyme‐linked immunosorbent assay, hematoxylin and eosin, immunohistochemistry, and western blot analysis assays in both cell and animal models. Sin reduced the cell viability of A549 and H1299, with the IC50 of 81.46 µM and 93.15 µM, respectively. Sin decreased invaded cell numbers, the expression of N‐cadherin and vascular endothelial growth factor A (VEGFA), while increased the E‐cadherin level, the cytotoxicity of CD8+ T cells, and the concentration of interferon‐γ (IFN‐γ), interleukin‐2 (IL‐2), and tumor necrosis factor‐α (TNF‐α) in NSCLC cells. Mechanistically, Sin declined the expression of protein kinase B (AKT)/β‐catenin pathway, which was restored with the application of SC79, an activator of AKT. The inhibitory role of Sin in NSCLC cell proliferation, invasion, epithelial‐mesenchymal transition (EMT) and immune escape was reversed by the management of SC79. In vivo, Sin reduced tumor size and weight, and the expression of N‐cadherin, VEGFA, and AKT/β‐catenin pathway, but enhanced the level of E‐cadherin and IFN‐γ. Taken together, Sin suppressed cell growth, invasion, EMT and immune escape via AKT/β‐catenin pathway in NSCLC.

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Sinensetin suppresses angiogenesis in liver cancer by targeting the VEGF/VEGFR2/AKT signaling pathway

Cited by 9 publications

References 53 publications

Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms

Sinensetin inhibits the movement ability and tumor immune microenvironment of non‐small cell lung cancer through the inactivation of AKT/β‐catenin axis

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