Rhaponticin suppresses the hypoxia-induced factor-1 alpha-mediated aggressive phenotype of tongue squamous cell carcinoma

Abstract

Background Emerging evidence suggests that rhaponticin, a stilbene monomeric compound isolated from North China rhubarb, has been shown to exhibit significant biological activity against tumors. However, the anticancer effects and mechanisms of rhaponticin in tongue squamous cell carcinoma (TSCC) remain elusive. Objective We investigated the changes of migration and invasion abilities and EMT progression of TSCC cells treated with different concentrations of rhaponticin under hypoxia, as well as the possible mechanisms, in order to initially explore the effects of rhaponticin on the biological characteristics of TSCC cells under hypoxia. Results The number of cell migration and invasion was prominently increased, E-cadherin protein was down-regulated, and N-cadherin and HIF-1α protein expression was elevated under hypoxia. Rhaponticin intervention strikingly prevented the increased abilities of migration and invasion and EMT of TSCC cells under hypoxia. This was followed by further validation finding that rhaponticin indeed leads to reduced HIF-1α post-transcriptional activity. Mechanistically, rhaponticin may bind to aryl-hydrocarbon nuclear translocator (ARNT) domain of HIF-1α. Conclusions Rhaponticin repressed the invasion and migration abilities and EMT process of TSCC cells under a hypoxic environment in vitro by targeted suppression of HIF-1α.

Resveratrol and Other Natural Oligomeric Stilbenoid Compounds and Their Therapeutic Applications

“…A more recent study highlighted that the stilbenoid glucoside rhaponticin inhibited benzo[a]pyrene-induced lung carcinogenesis in mice at 50 mg/kg bw, improving histopathological alterations and specific biomarkers levels [ 92 ]. Moreover, rhaponticin suppressed an osteosarcoma cell-based model by inhibiting the PI3K-Akt-mTOR pathway [ 93 ] and tongue squamous cell cancer aggressivity through inhibition of HIF-1α post-transcriptional activity [ 94 ].…”