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

Abstract

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.

Genistein Enhances or Reduces Glycosaminoglycan Quantity in a Cell Type-Specific Manner

“…It has been reported that genistein affects proliferations of oviductal epithelial cells [33], melanoma cells [34], telomerase-negative cells [35], and other cancer cells [36]. In consistent, current studies showed that genistein inhibited the proliferation of CHOK1, CHO3.1, CHO3.3 and HCT116 cells in a concentration-and time-dependent manner (Fig.…”

TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non‐small cell lung cancer patients

“…Our studies suggested that TIMM50 also promoted tumor proliferation and invasion in NSCLC cells via upregulating Cyclin D1 and Snail and downregulating E‐cadherin. During tumor progression, multiple signaling pathways, such as ERK, AKT, P38, and FAK, were involved in modulating the expression of Cyclin D1, Snail, and E‐cadherin . Using Western blotting analysis, we found that overexpression of TIMM50 was capable of upregulating the levels of phosphorylated ERK and P90RSK.…”

“…During tumor progression, multiple signaling pathways, such as ERK, AKT, P38, and FAK, were involved in modulating the expression of Cyclin D1, Snail, and E-cadherin. [14][15][16][17][18][19][20][21] Using Western blotting analysis, we found that overexpression of TIMM50 was capable of upregulating the levels of phosphorylated ERK and P90RSK. To further test the effect induced by overexpressing TIMM50 was mediated by activating ERK signaling pathway.…”

Oridonin inhibits migration, invasion, adhesion and TGF‑β1‑induced epithelial‑mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK‑3β signaling pathway

“…Cell migration wounding assay was performed according to the protocol described previously (25,26). A375 or B16-F10 cells were cultured in 60 mm dishes at the density of 8x10 5 cells/dish to 100% confluency.…”

“…Transwell assay (26,27). After pre-treatment with indicated concentrations of ORI for 24 h, A375 or B16-F10 cells were harvested and seeded to the upper chamber which was coated with matrigel (BD Biosciences) at the density of 3x10 4 cells/well in serum free medium.…”