3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo

Lu, Ko-Hsiu; Chen, Pei‐Ni; Hsieh, Yi‐Hsien; Chen, Lin; Cheng, Fu-Yuan; Chiu, Peng-Chou; Chu, Shu‐Chen; Hsieh, Yih‐Shou

doi:10.1016/j.fct.2016.09.006

Cited by 42 publications

(46 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence suggests that the FAK, MEK, and ERK signaling cascades play critical roles in regulating MMP gene transcription . In this study, we found that a FAK inhibitor, MEK inhibitors U0126 and PD98059, an ERK inhibitor and AP‐1 inhibitors curcumin and tanshinone all blocked IL‐1β‐increased MMP‐1 expression.…”

Section: Discussionmentioning

confidence: 57%

“…18 In the current study, we describe how Accumulating evidence suggests that the FAK, MEK, and ERK signaling cascades play critical roles in regulating MMP gene transcription. 35,36 In this study, we found that a FAK inhibitor, MEK inhibitors Cytokines, chemokines, and growth factors are known to regulate gene expression through the AP-1 site. 37,38 It has been reported that saponins reduce MMP-1 expression in immortalized human keratinocytes (HaCaT) via AP-1-dependent signaling 39 and that luteolin suppresses IL-1β-induced MMP production by inhibiting AP-1 activation.…”

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

Glucose suppresses IL‐1β‐induced MMP‐1 expression through the FAK, MEK, ERK, and AP‐1 signaling pathways

Lin

Tsai

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

Osteoarthritis (OA) commonly affects the synovial joint and is characterized by degradation of articular cartilage. Increased matrix metalloproteinase (MMP) activity plays a major role in this degradation. Dextrose (D-glucose) prolotherapy has shown promising activity in the treatment of different musculoskeletal disorders, including OA. However, little is known about the role of glucose on MMP inhibition in OA therapy. We found that stimulating chondrocytes with the proinflammatory cytokine interleukin-1β (IL-1β) increased the expression of MMP-1, MMP-3, and MMP-13. Glucose reduced this increase in MMP-1 expression, but had no effect upon MMP-3 or MMP-13 expression. Analyses using a focal adhesion kinase (FAK) inhibitor, MEK inhibitors (U0126 and PD98059), an ERK inhibitor, AP-1 inhibitors (curcumin and tanshinone), or siRNAs demonstrated that the FAK, MEK, ERK, and AP-1 pathways mediate IL-1β-induced increases in MMP-1 expression. Glucose antagonized IL-1β-promoted phosphorylation of FAK, MEK, ERK, and c-Jun. Thus, glucose decreased IL-1β-induced MMP-1 expression through the FAK, MEK, ERK, and AP-1 signaling cascades. These findings may provide a better understanding of the mechanisms of prolotherapy on inhibiting MMP expression.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 83%

Glucose suppresses IL‐1β‐induced MMP‐1 expression through the FAK, MEK, ERK, and AP‐1 signaling pathways

Lin

Tsai

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…MMP-2 and MMP-9 are considered the most vital enzymes that control the degradation of the main constituent of the ECM and are involved in osteosarcoma invasion, migration, and metastasis. [33][34][35][36]47 By inducing adhesion as a result of increasing E-cadherin and β1-integrin expression, 48 or decreasing MMP production, 50,51 melatonin inhibits the invasive activity of a wide range of tumors, including uveal melanoma, 52 osteosarcoma, 53 and breast, [54][55][56] gastrointestinal, 57 hematological, prostate, 58 ovary, 59 endometrium, 60 liver, 61 and brain cancers. 19,27,28,51,62,63 Initially, we speculated that the anti-metastatic effect of melatonin on U2OS and HOS cells was mediated by the inhibition of MMP-2 and MMP-9 activities; however, no direct evidence of this was observed (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Melatonin attenuates osteosarcoma cell invasion by suppression of C‐C motif chemokine ligand 24 through inhibition of the c‐Jun N‐terminal kinase pathway

Lin

et al. 2018

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

Osteosarcoma, with its high metastatic potential, is the most prevalent malignant bone tumor in children and adolescents. Melatonin possesses multiple tumor-suppressing properties for a myriad of tumors, but little is known about the effects of melatonin on osteosarcoma metastasis. In this study, we demonstrated that melatonin elicited very low cytotoxicity and significantly inhibited cellular motility, migration, and invasion in human osteosarcoma U2OS and HOS cells. Moreover, using RNA sequencing technology, we revealed that melatonin repressed C-C motif chemokine ligand 24 (CCL24) gene expression in U2OS cells. Manipulation of CCL24 levels influenced the motility of osteosarcoma cells as cell migration and invasion were enhanced by the addition of recombinant human CCL24 and attenuated by the silencing of CCL24. Moreover, melatonin increased and decreased the activation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2, respectively, in a dose-dependent manner in U2OS and HOS cells while exerting no evident influence on the level and activation of p38, Akt, FAK, steroid receptor coactivator, or Raf. In further functional experiments, the use of JNK inhibitors (SP600125 and DN-JNK) confirmed that the pharmaceutic inhibition of JNK augmented the melatonin-mediated CCL24 suppression and migration of U2OS cells. Overall, our results revealed that melatonin attenuated chemokine CCL24 levels through inhibition of the JNK pathway to hinder human osteosarcoma cell invasion, thereby highlighting the therapeutic potential of melatonin for osteosarcoma metastasis.

show abstract

“…In addition to secretion of MMPs and u‐PA, EMT activation decreased the expression level of E‐cadherin and increased those of vimentin and fibronectin . Studies have shown that reduced E‐cadherin expression is associated with progression and poor prognosis of prostate and breast cancers .…”

Section: Discussionmentioning

confidence: 99%

“…In addition to secretion of MMPs and u-PA, EMT activation decreased the expression level of E-cadherin and increased those of vimentin and fibronectin. 28,29 Studies have shown that reduced Ecadherin expression is associated with progression and poor prognosis of prostate 30 and breast cancers. 31 Moreover, noninvasive cancer cells can be activated by blocking the expression or knocking down of Ecadherin; meanwhile, invasive cancer cells can be inactivated by overexpressing E-cadherin.…”

Section: Discussionmentioning

confidence: 99%

Duchesnea indicaextract suppresses the migration of human lung adenocarcinoma cells by inhibiting epithelial-mesenchymal transition

Chen

Yang

et al. 2017

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is a process through which epithelial cells are transformed into mesenchymal cells; EMT diminishes cell polarity and cell-cell adhesion in cancer cells, leading to enhanced migratory and invasive properties. In this experiment, zymography, cell invasion, and migration assays were performed. Results indicated that Duchesnea indica extracts (DIE) inhibited highly metastatic A549 and H1299 cells by reducing the secretions of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Cell adhesion assay also demonstrated that DIE reduced the cell adhesion properties. Western blot analysis showed that DIE down-regulated the expression of N-cadherin, fibronectin, and vimentin, which are mesenchymal markers, and enhanced that of E-cadherin, which is an epithelial marker. In vivo study showed that tumor growth was significantly reduced in BALB/c nude mouse xenograft model administered with oral gavage of DIE. Therefore, DIE could be exhibits potential as a phytochemical-based platform for prevention and treatment of lung cancer. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2053-2063, 2017.

show abstract

3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo

Cited by 42 publications

References 45 publications

Glucose suppresses IL‐1β‐induced MMP‐1 expression through the FAK, MEK, ERK, and AP‐1 signaling pathways

Glucose suppresses IL‐1β‐induced MMP‐1 expression through the FAK, MEK, ERK, and AP‐1 signaling pathways

Melatonin attenuates osteosarcoma cell invasion by suppression of C‐C motif chemokine ligand 24 through inhibition of the c‐Jun N‐terminal kinase pathway

Duchesnea indicaextract suppresses the migration of human lung adenocarcinoma cells by inhibiting epithelial-mesenchymal transition

Contact Info

Product

Resources

About