PlatyphyllenoneExerts Anti-Metastatic Effects on Human Oral Cancer Cells by Modulating Cathepsin L Expression, MAPK Pathway and Epithelial–Mesenchymal Transition

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.

Cathepsins in oral diseases: mechanisms and therapeutic implications

“…The reduction of cathepsin L may affect the epithelial-tomesenchymal transition and have significant therapeutic implications for highly metastatic OSCC. However, more investigation is needed to figure out the exact mechanism (134). Besides, the inhibition of cathepsin S-induced autophagy in tumor cells could increase the expression of microtubule-associated protein I light chain 3 (LC3) protein, which may then cause the cytoplasmic form (LC3-I) to be cleaved and lapidated into LC3-II.…”

lncRNA DLEU2 Accelerates Oral Cancer Progression via miR-30a-5p/RAP1B Axis to Regulate p38 MAPK Signaling Pathway

“…In recent years, alterations in signaling pathways involved in OC have been shown to be important factors affecting OC development [ 15 , 16 ]. Among them, the canonical mitogen-activated protein kinase (MAPK) signaling pathway is considered to be involved in the growth and development of most cells [ 17 , 18 ]. As an important member of MAPK, phosphorylation of p38 MAPK mediates the migration and growth of OC cells [ 19 ].…”