Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-Mediated Pathway in Oral Squamous Cell Carcinoma

Abstract

This study aimed to investigate whether quercetin exerts anticancer effects on oral squamous cell carcinoma (OSCC) cell lines and to elucidate its mechanism of action. These anticancer effects in OSCC cells were assessed using an MTT assay, flow cytometry (to assess the cell cycle), wound-healing assay, invasion assay, Western blot analysis, gelatin zymography, and immunofluorescence. To investigate whether quercetin also inhibits transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human keratinocyte cells, HaCaT cells were treated with TGF-β1. Overall, our results strongly suggest that quercetin suppressed the viability of OSCC cells by inducing cell cycle arrest at the G2/M phase. However, quercetin did not affect cell viability of human keratinocytes such as HaCaT (immortal keratinocyte) and nHOK (primary normal human oral keratinocyte) cells. Additionally, quercetin suppresses cell migration through EMT and matrix metalloproteinase (MMP) in OSCC cells and decreases TGF-β1-induced EMT in HaCaT cells. In conclusion, this study is the first, to our knowledge, to demonstrate that quercetin can inhibit the survival and metastatic ability of OSCC cells via the EMT-mediated pathway, specifically Slug. Quercetin may thus provide a novel pharmacological approach for the treatment of OSCCs.Molecules 2020, 25, 757 2 of 15 Statistical AnalysesStatistical analyses were performed by a one-way analysis of variance (ANOVA) followed by a Bonferroni post-test, whereby three or more experimental groups were compared. p-values of < 0.05 were considered statistically significant. All data are the means ± standard error of the mean (SEM).

In Vitro Study of Two Edible Polygonoideae Plants: Phenolic Profile, Cytotoxicity, and Modulation of Keap1-Nrf2 Gene Expression

“…Considering the scarce data on chemical composition of P. amphibia [34,35,42,47] this work, with quantitative and tentative qualitative HPLC analysis, creates a notable contribution. cycle arrest [56][57][58]. Thus, quercetin caused the cell cycle arrest in G2/M phase, which was followed by a decrease in cell numbers in the G0/G1 phase [58].…”

Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers

“…Studies conducted on cell lines of neoplasms affecting the area of head and neck showed that these cells are sensitive to quercetin, and the sensitivity depends on the cell line, exposure time and quercetin concentration. It was demonstrated that is cytotoxically affects the following cell lines of the tongue cancer: SAS [ 51 , 52 , 53 , 54 ], OSC20 [ 52 ], SCC25 [ 48 , 55 , 56 ], SCC-9 [ 57 ], HSC-3 [ 58 , 59 ], Tca8113 [ 49 , 54 ], SCC-15 [ 49 ], TW206 [ 58 ]; throat cancer: FaDu line [ 59 ]; oral cavity cancer: HN22 [ 52 ] and TW206 [ 58 ] lines.…”

“…Inducing an inhibition of a cell cycle and apoptosis are well-known methods for treating some types of cancer. It was demonstrated that quercetin causes an increase in the percentage of cells in the G2/M phase of the cell cycle and a decrease in the percentage of cells in the G0/G1 phase [ 52 , 58 ]. After a treatment involving various doses of quercetin (25–75 μM), the percentage of cells in the G1 phase increases with a simultaneous decrease in the number of cells in the S phase and a gradual increase in the percentage of cells in the G1 phase with simultaneous increases in the cells in the sub-G phase, which indicates induction of apoptosis ( Figure 5 ) [ 55 ].…”

“…Quercetin also exerts an inhibiting effect on cell migration [ 52 , 53 ]. Dose-dependently, it increases expression of epithelial markers, such as E-cadherin and claudin-1, while simultaneously decreases the expression of mesenchymal markers, such as fibronectin, vimentin, and alpha-smooth muscle actin (α-SMA).…”

“…It reduces specific expression of mesenchymal markers in OSCC cells. EMT-activating transcription factors, such as Twist, Slug, and Snail 1 are significantly reduced after the use of quercetin [ 52 ].…”