Genistein induces morphology change and G2/M cell cycle arrest by inducing p38 MAPK activation in macrophages

Cui, Shuna; Wienhoefer, Nina; Bilitewski, Ursula

doi:10.1016/j.intimp.2013.11.016

Cited by 34 publications

(24 citation statements)

References 32 publications

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“…These results indicate that genistein exerts dual functions in regulating the MAPK cascade. It has been reported that genistein regulates the activation of MAPK in different cell types [50–52]. However, our results showed that genistein regulated MAPK in two different manners: stimulating the pathway at a lower concentration and inhibiting it at a higher concentration.…”

Section: Discussioncontrasting

confidence: 62%

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Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways

Cui

Wang

et al. 2017

Oncotarget

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Genistein is one of the main components of soy-based foods, which are widely known for their many benefits, including anti-cancer, anti-inflammatory, and antioxidant effects. In this study, we investigated the anti-metastasis effects of genistein on B16F10 melanoma cells. Our results showed that genistein strongly inhibited B16F10 cell proliferation and induced apoptosis in time- and concentration-dependent manners. Genistein altered the morphology of B16F10 cells to an elongated shape with slim pseudopodia-like protrusions. Moreover, genistein inhibited the invasion and migration abilities of B16F10 cells in a dose-dependent manner. On one hand, a high concentration of genistein (100 μM) significantly inhibited cell adhesion and migration, as shown by wound healing assays and transwell-migration and invasion assays. Furthermore, the expression levels of p-FAK, p-paxillin, tensin-2, vinculin, and α-actinin were decreased by genistein. As a result, genistein is believed to strongly downregulate the migration and invasion abilities of B16F10 cells via the FAK/paxillin pathway. Moreover, p-p38, p-ERK, and p-JNK levels were also dramatically decreased by treatment with genistein. Finally, genistein significantly decreased the gene expression of FAK, paxillin, vimentin, and epithelial-to-mesenchymal transition-related transcription factor Snail, as shown by real-time PCR (qPCR) analysis. On the other hand, a lower concentration of genistein (12.5 μM) significantly promoted both invasion and migration by activating the FAK/paxillin and MAPK signaling cascades. Taken together, this study showed for the first time that genistein exerts dual functional effects on melanoma cells. Our findings suggest that genistein regulates the FAK/paxillin and MAPK signaling pathways in a highly concentration-dependent manner. Patients with melanoma should therefore be cautious of consuming soy-based foods in their diets.

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Section: Discussioncontrasting

confidence: 62%

“…Western blot analysis was performed as described previously [50]. Cells were pretreated with or without DMSO (control) and genistein (12.5–100 μM) for 24 h. Cell lysates were prepared in ice-cold lysis buffer (MilliQ water + 100× Phosphatase and Protease Inhibitor Cocktail Set I).…”

Section: Methodsmentioning

confidence: 99%

Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways

Cui

Wang

et al. 2017

Oncotarget

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“…Then, we attempted to examine whether TSG was able to suppress the LPS stimulated activation and inflammation in RAW264.7 macrophages. It was known that macrophages exhibited a spreading and elongated morphology with pseudopodium-like protrusions after activation [26]. We defined the small round shaped cells as resting cells and the enlarged ones with protrusions as activated cells (Figure 1(c)).…”

Section: Resultsmentioning

confidence: 99%

HO-1 Is Essential for Tetrahydroxystilbene Glucoside Mediated Mitochondrial Biogenesis and Anti-Inflammation Process in LPS-Treated RAW264.7 Macrophages

Zhang

et al. 2017

Oxidative Medicine and Cellular Longevity

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2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an important monomer extracted from Polygonum multiflorum, can prevent a number of inflammation associated chronic diseases. However, the mechanism involved in TSG inducing anti-inflammatory role remains unclear. As an inducible antioxidant enzyme, Heme oxygenase-1 (HO-1), is crucial for protecting the mammalian cells against adverse stimuli. Here, we found that the TSG treatment strongly induces the expression of HO-1 in an NRF2-depended manner. Meanwhile, TSG increased the mitochondrial mass through upregulation of the mitochondrial biogenesis activators (PGC-1α, NRF1, and TFAM) as well as the mitochondrial complex IV. Furthermore, TSG attenuated Lipopolysaccharide (LPS) mediated RAW264.7 cells activation and secretion of proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Zinc Protoporphyrin (ZnPP), a selective inhibitor of HO-1 activity, was able to attenuate TSG mediated mitochondrial biogenesis and anti-inflammatory process. Finally, we observed that LPS induced obvious mtDNA depletion and ATP deficiency, which indicated a severe damage of mitochondria. TSG restored the LPS induced mitochondrial dysfunction via activation of the mitochondrial biogenesis. ZnPP treatment markedly reversed the inhibitory effects of TSG on mitochondrial damage and oxidative stress in LPS stimulated macrophages. Taken together, these findings suggest that TSG enhances mitochondrial biogenesis and function mainly via activation the HO-1. TSG can be developed as a potential drug for treatment of inflammatory diseases.

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“…CD11c hi MHC-II + cells are widely regarded to be DCs, but some macrophages can also display high amounts of these cell surface proteins (11, 49, 50). Similarly, some activated macrophages exhibit dendrite-like pseudopodia usually associated with DCs (51). Even the ability to activate naïve T cells, one of the functional definitions of DCs, can be observed for some macrophages (50).…”

Section: Discussionmentioning

confidence: 99%

Complement Receptor C5aR1/CD88 and Dipeptidyl Peptidase-4/CD26 Define Distinct Hematopoietic Lineages of Dendritic Cells

Nakano

Moran

Nakano

et al. 2015

The Journal of Immunology

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Differential display of the integrins CD103 and CD11b are widely used to distinguish two major dendritic cell (DC) subsets in nonlymphoid tissues. CD103+ DCs arise from fms-like tyrosine kinase receptor 3 (FLT3)-dependent DC precursors (preDC), whereas CD11bhi DCs can arise either from preDCs or FLT3-independent monocytes. Functional characterization of these two lineages of CD11bhi DCs has been hindered by the lack of a widely applicable method to distinguish between them. We performed gene expression analysis of fractionated lung DCs from C57BL/6 mice, and found that monocyte-derived (mo)DCs including CD11bhiLy-6Clo tissue resident and CD11bhiLy-6Chi inflammatory moDCs express the complement 5a receptor 1 (C5aR1)/CD88, whereas preDC-derived conventional DCs (cDCs) including CD103+ and CD11bhi cDCs express dipeptidyl peptidase-4/CD26. Flow cytometric analysis of multiple organs, including the kidney, liver, lung, lymph nodes, small intestine and spleen, confirmed that reciprocal display of CD88 and CD26 can reliably distinguish FLT3-independent moDCs from FLT3-dependent cDCs in C57BL/6 mice. Similar results were obtained when DCs from BALB/c mice were analyzed. Using this novel approach to study DCs in mediastinal lymph nodes, we observed that the majority of blood-derived LN resident DCs, as well as tissue-derived migratory DCs, are cDCs. Furthermore, cDCs, but not moDCs, stimulated naïve T cell proliferation. We anticipate that the use of antibodies against CD88 and CD26 to distinguish moDCs and cDCs in multiple organs and mouse strains will facilitate studies aimed at assigning specific functions to distinct DC lineages in immune responses.

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Genistein induces morphology change and G2/M cell cycle arrest by inducing p38 MAPK activation in macrophages

Cited by 34 publications

References 32 publications

Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways

Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways

HO-1 Is Essential for Tetrahydroxystilbene Glucoside Mediated Mitochondrial Biogenesis and Anti-Inflammation Process in LPS-Treated RAW264.7 Macrophages

Complement Receptor C5aR1/CD88 and Dipeptidyl Peptidase-4/CD26 Define Distinct Hematopoietic Lineages of Dendritic Cells

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