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.
Highlights
Oral squamous cell carcinoma (OSCC) is the most common malignancy, accounting for about90% of head and neck cancers, and develops at the lips, tongue, salivary glands, gums, bottom of the mouth, pharynx, and surfaces within the oral cavity [1,2,3,4,5,6]
The results showed that quercetin decreased cell viability in OSCC cell lines (Figure 1A)
To determine the function of quercetin in the regulation of the cell cycle, OSCC cell lines were stimulated with low levels of quercetin (10–40 μM) for 24 h and analyzed the distribution of the cell cycle using flow cytometry
Summary
Oral squamous cell carcinoma (OSCC) is the most common malignancy, accounting for about. 90% of head and neck cancers, and develops at the lips, tongue, salivary glands, gums, bottom of the mouth, pharynx, and surfaces within the oral cavity [1,2,3,4,5,6]. OSCC, an aggressive human cancer with the highest mortality, has a significant impact on the quality of life of patients [6,7]. OSCC is treated with a combination of surgery and radiation therapy; this strategy does not significantly increase survival in OSCC patients. Many studies have focused on compounds derived from natural products as potential candidate agents for treating or preventing OSCCs. OSCC is known to have multifactorial etiologies, including tobacco, alcohol, and viruses [6,8,9,10].
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