Plumbagin inhibits tumor angiogenesis of gastric carcinoma in mice by modulating nuclear factor-kappa B pathway

Cheng-Qian, Yang; Feng, Xingbo; Li, Zengxian; He, Qingsi

doi:10.21037/tcr.2019.12.03

Cited by 6 publications

(6 citation statements)

References 21 publications

(34 reference statements)

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“…Because of the heterogeneity and plasticity of macrophages, their phenotype and function are regulated by the surrounding microenvironment. It has been shown that GC‐exo induce the M2 phenotype differentiation of macrophages by activating the NF‐κB pathway 38 . In addition, GC‐exo can polarize monocytes into PD‐1 + ‐tumor‐associated macrophages with an immunosuppressive phenotype and function to promote GC progression 21 .…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that GCexo induce the M2 phenotype differentiation of macrophages by activating the NF-κB pathway. 38 In addition, GCexo can polarize monocytes into PD-1 + -tumor-associated macrophages with an immunosuppressive phenotype and function to promote GC progression. 21 In the present study, we found MFC-exo induced the lung macrophage expression of PD-L1 and led to pulmonary metastasis.…”

Section: Discussionmentioning

confidence: 99%

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Gastric cancer‐derived exosomes facilitate pulmonary metastasis by activating ERK‐mediated immunosuppressive macrophage polarization

Chu

Huo

et al. 2023

J of Cellular Biochemistry

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Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reversetranscription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signalregulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gastric cancer‐derived exosomes facilitate pulmonary metastasis by activating ERK‐mediated immunosuppressive macrophage polarization

Chu

Huo

et al. 2023

J of Cellular Biochemistry

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“…Some reports showed that inhibition of NF-kappa B signal pathways can promote apoptosis [ 43 ]. Previously, it was shown showed that plumbagin inhibits tumor cell proliferation of gastric cancer through the NF-kappa B pathway [ 44 ]. NF-kappa B was down-regulated with CHSP treatment, showing that similar to PTEN, promotion of apoptosis and anti-proliferation in ovarian cancer cells may also be attributed to the down-regulation of NF-kappa B protein.…”

Section: Discussionmentioning

confidence: 99%

Polyphenols Extracted from Chinese Hickory (Carya cathayensis) Promote Apoptosis and Inhibit Proliferation through the p53-Dependent Intrinsic and HIF-1α-VEGF Pathways in Ovarian Cancer Cells

Lin

et al. 2020

Applied Sciences

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Ovarian cancer is the second most common gynecologic cancer with an estimated 13,940 mortalities across the United States in 2020. Natural polyphenols have been shown to double the survival time of some cancer patients due to their anticancer properties. Therefore, the effect of polyphenols extracted from Chinese hickory seed skin Carya cathayensis (CHSP) on ovarian cancer was investigated in the present study. Cell viability results showed that CHSP is more effective in inhibiting ovarian cancer cells than normal ovarian cells, with the IC50 value for inhibition of cell proliferation of Ovarian cancer cells (OVCAR-3) being 10.33 ± 0.166 µg/mL for a 24 h treatment. Flow cytometry results showed that the apoptosis rate was significantly increased to 44.21% after 24 h treatment with 20 µg/mL of CHSP. Western blot analysis showed that CHSP induced apoptosis of ovarian cancer cells through a p53-dependent intrinsic pathway. Compared with control values, levels of VEGF excreted by OVCAR-3 cancer cells were reduced to 7.87% with a 40 µg/mL CHSP treatment. Consistent with our previous reports, CHSP inhibits vascular endothelial growth factor (VEGF) secretion by regulating the HIF-1α-VEGF pathway. In addition, we also found that the inhibitory effect of CHSP on ovarian cancer is related to the up-regulation of Phosphatase and tension homolog (PTEN) and down-regulation of nuclear factor kappa-B (NF-kappa B). These findings provide some evidence of the anti-ovarian cancer properties of CHSP and support the polyphenols as potential candidates for ovarian cancer adjuvant therapy.

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“… 9 PLB may be an effective drug in inhibiting the tumor angiogenesis of gastric cancer and the mechanism of anti-tumor may be associated with NF-κB pathway. 10 …”

Section: Introductionmentioning

confidence: 99%

“…9 PLB may be an effective drug in inhibiting the tumor angiogenesis of gastric cancer and the mechanism of anti-tumor may be associated with NF-κB pathway. 10 Tazemetostat (EPZ-6438, Figure 1A), a first-in-class small molecule enhancer of zeste homolog 2 (EZH2) inhibitor, is developed by Epizyme in collaboration with Eisai, and it is the first therapy to be approved specifically for the treatment of epithelioid sarcoma. 11 Tazemetostat was another important supplement for the treatment of patients with relapsed or refractory follicular lymphoma (R/R FL), it likely helps improve the development trajectory of the disease.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Herb-Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS

Li¹,

Wang²,

Geng³

et al. 2022

DDDT

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Objective A sensitive and rapid UPLC-MS/MS method for determination of tazemetostat in rat plasma was developed, and the pharmacokinetics of herb-drug interactions (HDIs) of plumbagin (PLB) and tazemetostat was investigated. Methods After the rat plasma samples were precipitated by acetonitrile, tazemetostat and verubecestat (ISTD) were detected. Gradient elution was performed with 0.1% formic acid and acetonitrile as mobile phases. The multi-reaction monitoring was used with ESI+ source, and the ion pairs for tazemetostat and ISTD were m/z 573.12→135.99 and m/z 410.10→124.00, respectively. 12 SD rats were randomly divided into the control group and the experimental group, 6 rats in each group. The rats in the experimental group were given PLB 100 mg/kg by gavage once a day for 7 consecutive days. The rats in the control group were given the same amount of 0.1% sodium carboxymethyl cellulose solution by gavage once a day for 7 consecutive days. At the seventh day, tazemetostat (80 mg/kg) was given and the blood was collected at different time points. The main parameters of pharmacokinetics were calculated and the herb-drug interactions (HDIs) were evaluated. Results In the calibrated range of 1–1000 ng/mL, tazemetostat had a good linearity. The extraction recovery was more than 84%, and the RSD of intra-batch and inter-batch precision were both less than 15%. The C max of tazemetostat in the experimental group was 32.48% higher than that in the control group, and the AUC (0-t) and AUC (0−∞) of tazemetostat in the experimental group were 46.24% and 46.67% higher than that in the control group, respectively, and the t 1/2 was prolonged from 10.56 h to 11.73 h. Conclusion A simple, rapid and sensitive UPLC-MS/MS method for the determination of tazemetostat in rat plasma was established. PLB can inhibit the metabolism of tazemetostat and increase the plasma exposure of tazemetostat in rats.

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Plumbagin inhibits tumor angiogenesis of gastric carcinoma in mice by modulating nuclear factor-kappa B pathway

Cited by 6 publications

References 21 publications

Gastric cancer‐derived exosomes facilitate pulmonary metastasis by activating ERK‐mediated immunosuppressive macrophage polarization

Gastric cancer‐derived exosomes facilitate pulmonary metastasis by activating ERK‐mediated immunosuppressive macrophage polarization

Polyphenols Extracted from Chinese Hickory (Carya cathayensis) Promote Apoptosis and Inhibit Proliferation through the p53-Dependent Intrinsic and HIF-1α-VEGF Pathways in Ovarian Cancer Cells

Pharmacokinetics of Herb-Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS

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