Abstract
Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased β-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial–mesenchymal transition process.
Highlights
Because platyphyllenone did not exhibit any anti-proliferative effect, we thought of investigating the anti-migratory effects of platyphyllenone on human oral cancer cells using wound closer assay
By conducting transwell migration and invasion assays using cathepsin L-overexpressed, platyphyllenone-treated cells, we observed that overexpression of cathepsin L significantly increased the migration and invasion of oral cancer cells, and that the anti-migratory/anti-invasive effects of platyphyllenonewere diminished by cathepsin L overexpression (Figure 7E,F)
We evaluated the effects of platyphyllenone, a plant-derived diarylheptanoid derivative, in modulating the proliferation, migration, and invasion of human oral cancer cells
Summary
Important cellular components of the MAPK signaling pathway, including ERK1/2, JNK, and p38, play vital roles in regulating many physiological processes, such as cell proliferation, apoptosis, angiogenesis, and migration [4]. Given the significant involvement of MAPK signaling in neoplastic transformation, severe small molecular inhibitors targeting specific components of the pathway have been identified, and the majority of the inhibitors have shown promising anti-cancer effects in clinical trials [5,6,7]. In case of oral squamous cell carcinoma, certain bioactive plant compounds, such as epigallocatechin-3-gallate, S-allylcysteine, pterostilbene, and resveratrol, have been shown to inhibit cancer cell proliferation, induce apoptosis, and inhibit migration by modulating the MAPK signaling pathway [8,9,10,11]
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