Effects of 6,8-Diprenylgenistein on VEGF-A-Induced Lymphangiogenesis and Lymph Node Metastasis in an Oral Cancer Sentinel Lymph Node Animal Model

Bae, Mun Gyeong; Jeon, Hoon; Lee, Dong Hoon; Lee, Youn‐Hyung; Chung, In Sik

doi:10.3390/ijms22020770

Cited by 11 publications

(11 citation statements)

References 30 publications

(47 reference statements)

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“…RASE1 reduced VEGFR-2 and VE-cadherin complex expression via NF- κ B downregulation, which are important growth factors for proliferation and vascular remodeling. Various growth factors have been documented to play an important role in PI3K/AKT and ERK pathway activation [ 61 ]. RT-PCR results showed AKT and ERK mRNA level inhibition via VEGFR-2 downregulation in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways

Khan

Shin

et al. 2021

BioMed Research International

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Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1) in vitro in human umbilical vein endothelial cells (HUVECs), 3T3-L1 preadipocytes respectively, and in vivo using a high-fat and carbohydrate diet-induced obesity mouse model. Orlistat was used as a positive control, while untreated cells and animals were normal controls (NCs). Adipose tissue, liver, and blood were analyzed after dissection. Extracted stevia compounds and green tea seed saponin E1 exhibited pronounced antiobesity effects when combined. RASE1 inhibited HUVEC proliferation and tube formation by suppressing VEGFR2, NF-κB, PIK3, and-catenin beta-1 expression levels. RASE1 inhibited 3T3-L1 adipocyte differentiation and lipid accumulation by downregulating adipogenesis- and lipogenesis-promoting genes. RASE1 oral administration reduced mouse body and body fat pad weight and blood cholesterol, TG, ALT, AST, glucose, insulin, and adipokine levels. RASE1 suppressed adipogenic and lipid metabolism gene expression in mouse adipose and liver tissues and enhanced AMP-activated protein kinase levels in liver and adipose tissues and in serum adiponectin. RASE1 suppressed the NF-κB pathway and proinflammatory cytokines IL-10, IL-6, and TNF-α levels in mice which involve inflammation and progression of obesity. The overall results indicate RASE1 is a potential therapeutic formulation and functional food for treating or preventing obesity and inflammation.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways

Khan

Shin

et al. 2021

BioMed Research International

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“…Similarly, 6,8-Diprenylgenistein (6,8-DG), an isoflavonoid isolated from Cudrania tricuspidata has been reported with its inhibitory effect on VEGF-A induced lymphangiogenesis as well. In the oral cancer model, 6,8-DG inhibited VEGF-A expression and blocked the VEGFR-2 interaction with VEGF-A, decreasing cervical lymph nodes metastasis of the oral squamous cell carcinoma ( 101 ). Newly examined histone deacetylase inhibitors Trichostatin A (TSA) ( 100 ) and Dimethyl fumarate (DMF) ( 94 ) both caused G1 cell cycle arrest in a p21-dependent manner.…”

Section: Drugs Targeting Tumor Lymphangiogenesismentioning

confidence: 99%

Advances in Drugs Targeting Lymphangiogenesis for Preventing Tumor Progression and Metastasis

Wang

Chu

2022

Front. Oncol.

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Metastasis of cancer cells from the primary tumor to other organs and tissues in the body is the leading cause of death in patients with malignancies. One of the principal ways cancer cells travel is through lymphatic vessels, and tumor invasion into the regional lymph nodes is a hallmark of early metastasis; thus, the formation of especially peritumoral lymphatic vessels is essential for tumor transportation that gives rise to further progression. In the past few decades, tumor-induced lymphangiogenesis has been testified to its tight correlation with lymphatic metastasis and poor clinical outcomes in multiple types of human malignancies, which warrants novel potential therapeutic targets for cancer treatment. As the understanding of underlying molecular mechanisms has grown tremendously over the years, an inexorable march of anti-lymphangiogenic therapy also aroused terrific interest. As a result, a great number of drugs have entered clinical trials, and some of them exhibited predominant contributions in cancer management. Herein, this review provides an updated summary of the current advances in therapies preventing lymphatic metastasis and discusses the validity of different applications.

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“…In female BALB/c mice with sentinel lymph node from VEGF‐A‐induced oral cancer, treatment with a natural derivative of genistein (6,8‐diprenylgenisteine) at a dose of 2.5 mg/kg every 2 days for 14 days by intraperitoneal injection suppressed lymph node metastasis, suggesting that the effect was by inhibition in VEGFR‐2 signaling (Bae et al, 2021).…”

Section: Antiinvasive Action Of Isoflavonoidsmentioning

confidence: 99%

Natural isoflavonoids in invasive cancer therapy: From bench to bedside

Cayetano-Salazar

Olea-Flores

Zuñiga-Eulogio

et al. 2021

Phytotherapy Research

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Cancer is a public health problem worldwide, and one of the crucial steps within tumor progression is the invasion and metastasis of cancer cells, which are directly related to cancer‐associated deaths in patients. Recognizing the molecular markers involved in invasion and metastasis is essential to find targeted therapies in cancer. Interestingly, about 50% of the discovered drugs used in chemotherapy have been obtained from natural sources such as plants, including isoflavonoids. Until now, most drugs are used in chemotherapy targeting proliferation and apoptosis‐related molecules. Here, we review recent studies about the effect of isoflavonoids on molecular targets and signaling pathways related to invasion and metastasis in cancer cell cultures, in vivo assays, and clinical trials. This review also reports that glycitein, daidzein, and genistein are the isoflavonoids most studied in preclinical and clinical trials and displayed the most anticancer activity targeting invasion‐related proteins such as MMP‐2 and MMP‐9 and also EMT‐associated proteins. Therefore, the diversity of isoflavonoids is promising molecules to be used as chemotherapeutic in invasive cancer. In the future, more clinical trials are needed to validate the effectiveness of the various natural isoflavonoids in the treatment of invasive cancer.

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Effects of 6,8-Diprenylgenistein on VEGF-A-Induced Lymphangiogenesis and Lymph Node Metastasis in an Oral Cancer Sentinel Lymph Node Animal Model

Cited by 11 publications

References 30 publications

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways

Advances in Drugs Targeting Lymphangiogenesis for Preventing Tumor Progression and Metastasis

Natural isoflavonoids in invasive cancer therapy: From bench to bedside

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