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.
Highlights
Melanomas are malignant skin tumors that have a poor cure rate because of their invasive behavior
We evaluated the influence of genistein, at various concentrations and incubation times, on the viability of melanoma cells using the WST-8 assay
We found that only the highest concentration of genistein evaluated (100 μM) significantly inhibited the growth of B16F10 cells after 24 and 48 h of incubation
Summary
Melanomas are malignant skin tumors that have a poor cure rate because of their invasive behavior. Tyrosine kinase inhibitors and immunomodulating agents are widely used in clinical therapy. These agents are associated with high incidences of adverse and toxic effects [1, 2]. A complex process involving cell migration, adhesion, and invasiveness, is often associated with melanomas. Benign tumor cells acquire the ability to migrate and invade, which are important steps in their www.impactjournals.com/oncotarget transformation into malignant cancer cells. Cell migration is a dynamic and multistep process involving leading edge protrusion, turnover of focal adhesions, generation of traction forces, and tail retraction and detachment [3, 4]. Various types of highly mobile cancer cells share certain features, such as epithelial-to-mesenchymal cell transition, the formation of filopodia or lamellipodia, and changes in cytoskeleton structure and morphology [7,8,9]
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