Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

Fukuda, Hiroki; Nakamura, Seikou; Chisaki, Yugo; Takada, Tetsuya; Toda, Yuki; Murata, Hiroaki; Itoh, Kazuyuki; Yano, Yoshitaka; Takata, Kazuyuki; Ashihara, Eishi

doi:10.1016/j.bbrc.2016.01.179

Cited by 33 publications

(21 citation statements)

References 21 publications

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“…In osteosarcoma, our observation that RhoA is suppressed after depleting Skp2 is consistent with previous reports. Since the RhoA GTPase plays a crucial role in the invasiveness and metastasis of multiple cancers 29 , 33 – 37 , it is likely that FKA or Skp2 knockdown blocks RhoA, leading to inhibition of invasiveness and lung metastasis in osteosarcoma. Furthermore, previous studies have shown that Skp2 promotes the expression of matrix metalloproteinase (MMP) 14 , thus enhancing metastatic potential 38 .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma

Zhang

Zvi

Batko

et al. 2018

Sci Rep

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Osteosarcoma (OS), the most common primary cancer of bone, exhibits a high propensity for local invasion and distant metastasis. This study sought to elucidate the role of S phase kinase-associated protein (Skp2) in osteosarcoma invasion and metastasis and to explore flavokawain A (FKA), a natural chalcone from kava extract, as a potential Skp2 targeting agent for preventing osteosarcoma progression. Skp2 was found to be overexpressed in multiple osteosarcoma cell lines, including 5 standard and 8 primary patient-derived cell lines. Patients whose tumors expressed high levels of Skp2 sustained a significantly worse metastasis-free (p = 0.0095) and overall survival (p = 0.0013) than those with low Skp2. Skp2 knockdown markedly reduced in vitro cellular invasion and in vivo lung metastasis in an orthotopic mouse model of osteosarcoma. Similar to Skp2 knockdown, treatment with FKA also reduced Skp2 expression in osteosarcoma cell lines and blocked the invasion of osteosarcoma cells in vitro and lung metastasis in vivo. Together, our findings suggest that Skp2 is a promising therapeutic target in osteosarcoma, and that FKA may be an effective Skp2-targeted therapy to reduce osteosarcoma metastasis.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma

Zhang

Zvi

Batko

et al. 2018

Sci Rep

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“…As the most well-known Rho family member, Rac1 has been reported to inhibit RA-FLS proliferation and invasion ( Liang et al, 2013 ). Previous studies have indicated that downregulation of RhoA and Cdc42 inhibits the invasion and migration of osteosarcoma cells ( Fukuda et al, 2016 ). The present study showed that miR-27a suppressed expression of MMPs and Rho family members and inhibited RA-FLS migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis

Shi¹,

Shi²,

Xie³

et al. 2016

Molecules and Cells

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Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA) are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key role in RA development. The results of a Transwell assay showed that miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition promoted the migration and invasion of FLS. In addition, the down-regulated expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then, a luciferase reporter assay validated that miR-27a targeted the 3-untranslated region (3′-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of FSTL1. In addition, the expression of TLR4 and NFκB was inhibited by miR-27a but increased by FSTL1 overexpression. In conclusion, we found that miR-27a inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the TLR4/NFκB pathway.

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“…It has been clinically used in the treatment of rheumatoid arthritis, lumbago, and coagulation disorders and as an antipyretic [125][126][127]. It possesses multiple pharmacological properties, including anti-inflammatory and oxidant activities [128,129], and demonstrated a significant anticancer effect in vitro [130,131]. In a rat model of collagen-induced arthritis, daphnetin suppressed joint destruction, synovial hyperplasia, and Th1/Th2/Th17-type cytokines in splenic lymphocytes and increased the expression of Foxp3 [125], demonstrating a potent anti-inflammatory activity.…”

Section: Urolithin Amentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

158

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

Cited by 33 publications

References 21 publications

Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma

Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma

MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

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