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

        Wu Yuan,Wan Xiaowen,Shao Yisen,Wang Wei,Huang Wenquan,Zhu Jiajun,Jiang Lin 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.2

        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.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.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.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. 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.

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