Methanol extract of Codium fragile inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation

Dilshara, Matharage Gayani; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Kang, Chang‐Hee; Choi, Yung Hyun; Kim, Gi‐Young

doi:10.1016/j.apjtm.2016.04.010

Cited by 15 publications

(11 citation statements)

References 24 publications

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“…Hence, MMP-9 is not only critical in recognizing signs of invasion and diagnosis, but also a promising therapeutic target to prevent invasion and metastasis of cancer. 36 Furthermore, the significant increase (P < .05) in NO concentration of EAC-bearing mice might be due to TNFα overexpression. It has been demonstrated that TNF-α is a mediator of NO synthesis.…”

Section: Discussionmentioning

confidence: 97%

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Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-Irradiated Solid Ehrlich Carcinoma-Bearing Mice

et al. 2020

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Pathological angiogenesis and apoptosis evasion are common hallmarks of cancer. The present work was an endeavor to evaluate the influence of bee venom (BV) or its major constituent melittin (MEL) as antiapoptotic and angiogenic regulator modifier on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. BV (0.56 mg/kg/day) and MEL (500 µg/kg body weight/day) were injected intraperitoneally to mice bearing 1 cm3 solid tumor of Ehrlich ascites carcinoma (EAC) for 21 consecutive days. Mice were whole-body exposed to 1 Gray (Gy) of γ-radiation (2 fractionated doses). Treatment with BV or MEL markedly suppresses the proliferation of tumor in EAC mice. The concentrations of m-RNA for angiogenic factors (TNF-α, VEGF) as well as MMPs 2 and 9 activities and NO concentration were significantly decreased, combined with improvements in apoptotic regulators (caspase-3 activity) and normal cells redox tone (catalase and free radicals content) compared with EAC mice. Moreover, the histopathological investigation confirms the improvement exerted by BV or MEL in the EAC mice group or EAC + R group. Exposure to γ-radiation sustained the modulatory effect of BV on tumor when compared with EAC + BV mice. Convincingly, the role of BV or MEL as a natural antiangiogenic in the biological sequelae after radiation exposure is verified. Hence, BV and its major constituent MEL might represent a potential therapeutic strategy for increasing the radiation response of solid tumors.

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Section: Discussionmentioning

confidence: 97%

“…Hence, MMP-9 is not only critical in recognizing signs of invasion and diagnosis, but also a promising therapeutic target to prevent invasion and metastasis of cancer. 36 …”

Section: Discussionmentioning

confidence: 99%

Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-Irradiated Solid Ehrlich Carcinoma-Bearing Mice

et al. 2020

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“…However, few studies have reported on some marine algae and their probable antithrombotic effects (Trento et al, 2001). In the present study, therefore, we evaluated the antithrombotic properties of Codium fragile (Suringar) Hariot, which has been used as a therapeutic agent for its anti-inflammatory and antioxidant effects in traditional medicine (Lee et al, 2013;Dilshara et al, 2016). We demonstrated that treatment with C. fragile inhibits thrombus formation in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 89%

“…In Korea, C. fragile has been used as a culinary ingredient and traditional medicine to treat enterobiasis, dropsy, and dysuria (Lehnhardt Pires et al, 2013). Several studies have indicated a protective effect of C. fragile against pro-inflammatory stimuli, oxidative damage, and tumor progression in experimental models (Kang et al, 2012;Lee et al, 2013;Dilshara et al, 2016). Sterol-based compounds with varying bioactivities were identified as the main components of C. fragile extract (Rubinstein and John Goad, 1974;Lee et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Extract of Seaweed Codium fragile Inhibits Integrin αIIbβ3-Induced Outside-in Signaling and Arterial Thrombosis

Kim

2021

Front. Pharmacol.

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Seaweeds are thought to be promising candidates for functional foods and to help prevent thrombotic and related cardiovascular diseases. Codium fragile (Suringer) Hariot has been traditionally used as a culinary ingredient, and it possesses a range of biological activities, including the inhibition of platelet function. However, the mechanism of this inhibition is unclear. The aim of this study was to examine the inhibitory effect of C. fragile in platelet function. The antiplatelet activity of C. fragile on agonist-activated platelet aggregation, granule secretion, calcium mobilization, platelet spreading, and clot retraction was assessed. The phosphorylation of c-Src, Syk, PLCγ2, and several proteins involving in the αIIbβ3 integrin outside-in signaling pathway were also studied in thrombin and CRP-stimulated platelets. The antithrombotic effect was investigated in mice using ferric chloride-induced arterial thrombus formation in vivo. Transection tail bleeding time was used to evaluate whether C. fragile inhibited primary hemostasis. The main components and contents of C. fragile ethanol extract were confirmed by GC-MS analysis. C. fragile significantly impaired agonist-induced platelet aggregation granule secretion, calcium mobilization, platelet spreading, and clot retraction. Biochemical analysis revealed that C. fragile inhibited the agonist-induced activation of c-Src, Syk, and PLCγ2, as well as the phosphorylation of PI3K, AKT, and mitogen-activated protein kinases (MAPKs). The inhibitory effect of C. fragile resulted from an inhibition of platelet αIIbβ3 integrin outside-in signal transduction during cell activation. Oral administration of C. fragile efficiently blocked FeCl3-induced arterial thrombus formation in vivo without prolonging bleeding time. GC-MS analysis revealed that phytol was the main constituent and the total content of isomers was 160.8 mg/kg. Our results demonstrated that C. fragile suppresses not only the inside-out signaling of αIIbβ3 integrin but also outside-in signal transmission. Therefore, C. fragile could be an effective antiplatelet therapeutic candidate.

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“…Therefore, MMP-9 is not only important in identifying invasion symptoms and diagnosis, but also a promising therapeutic target to prevent cancer invasion and metastasis. 49 A mutual relationship between STAT signaling and MMP-2 was previously demonstrated, where overexpression of STAT3 enhances the invasiveness in less-invasive melanoma cells through increasing MMP-2 expression and activity, while inactivation of STAT3 remarkably impairs the invasive ability of invasive melanoma cells through decreasing MMP-2 expression and activity. 50 In addition, TNF-α has already been shown to be involved in cell-cell communication, and in a coculture of breast cancer cells and tumor-associated macrophages, macrophage-derived TNF-α increased the levels of MMP-2 and MMP-9 in tumor cells.…”

Section: Discussionmentioning

confidence: 97%

Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice

et al. 2017

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Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.

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Methanol extract of Codium fragile inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation

Abstract: MECF exhibited its anti-invasive capability by downregulating TNF-α-induced MMP-9 expression, resulting from the suppression of NF-κB activity in the human breast cancer cell line MDA-MB-231.

Cited by 15 publications

References 24 publications

Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-Irradiated Solid Ehrlich Carcinoma-Bearing Mice

Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-Irradiated Solid Ehrlich Carcinoma-Bearing Mice

Extract of Seaweed Codium fragile Inhibits Integrin αIIbβ3-Induced Outside-in Signaling and Arterial Thrombosis

Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice

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