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Piperlongumine Inhibits OSCC Epithelial-Mesenchymal Transition and Promotes Tumor Cell Apoptosis by Targeting TrxR1
Mingxing Tian1,2, Chao Deng1,2, Detao Tao1,3
1School of Stomatology, Wannan Medical College.
Abstract:
Piperlongumine (PL), a naturally occurring alkaloid isolated from Piper longum fruit, has been shown to selectively toxinate a variety of tumor cells. However, PL has received less attention when it comes to oral squamous cell carcinoma (OSCC), and its precise effects and mechanisms have not been completely clarified. We verified that thioredoxin reductase 1 (TrxR1) is highly expressed in OSCC cell lines and cancer tissues of OSCC patients; PL inhibited TrxR1 activity in a concentration-dependent manner; PL inhibited OSCC cells in a concentration-dependent manner, and the inhibitory effect was more pronounced in TrxR1 low-regulated expression cells; PL could cause an increase in the level of reactive oxygen specie (ROS) in OSCC cells, and the effect was more pronounced in TrxR1 low-expression OSCC cells; PL inhibited the activation of the WNT pathway to prevent the occurrence of the epithelial-mesenchymal transition (EMT) in OSCC cells; PL activated the activation of the mitochondrial apoptotic pathway to promote the occurrence of OSCC apoptosis; and both the inhibition of the WNT pathway and the activation of the mitochondrial apoptosis by PL could be reversed by the ROS scavenger GSH. In conclusion, our research shows that PL inhibits the activity of TrxR1 in OSCC cells, increasing the level of ROS, which in turn inhibits EMT and promotes apoptosis in tumor cells by blocking the WNT pathway and activating the mitochondrial apoptosis pathway.
Insights
Piperlongumine (PL) effectively targets oral squamous cell carcinoma (OSCC) by inhibiting thioredoxin reductase 1 (TrxR1) and increasing reactive oxygen species (ROS). This action suppresses tumor cell growth, epithelial-mesenchymal transition (EMT), and promotes apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Piperlongumine (PL), a natural alkaloid, shows anti-cancer properties but its role in oral squamous cell carcinoma (OSCC) is underexplored.
- Thioredoxin reductase 1 (TrxR1) is highly expressed in OSCC, suggesting it as a potential therapeutic target.
Purpose of the Study:
- To investigate the precise effects and mechanisms of Piperlongumine (PL) in oral squamous cell carcinoma (OSCC).
- To determine the role of thioredoxin reductase 1 (TrxR1) in PL's anti-cancer activity against OSCC.
Main Methods:
- Assessed TrxR1 expression in OSCC cell lines and patient tissues.
- Evaluated PL's effect on TrxR1 activity, OSCC cell viability, and reactive oxygen species (ROS) levels.
- Investigated PL's impact on the WNT pathway, epithelial-mesenchymal transition (EMT), and mitochondrial apoptosis pathway.
- Utilized ROS scavenger (GSH) to confirm mechanisms.
Main Results:
- PL inhibited TrxR1 activity and OSCC cell growth in a concentration-dependent manner, with greater effect in TrxR1 low-expression cells.
- PL increased ROS levels in OSCC cells, particularly in TrxR1 low-expression cells.
- PL suppressed WNT pathway activation, preventing EMT, and activated mitochondrial apoptosis.
- ROS scavenging reversed PL's effects on WNT and apoptosis.
Conclusions:
- Piperlongumine (PL) exerts anti-cancer effects in OSCC by inhibiting TrxR1 and increasing ROS.
- PL's mechanism involves suppressing the WNT pathway, inhibiting EMT, and promoting apoptosis via mitochondrial pathways.
- PL demonstrates potential as a therapeutic agent for OSCC, targeting TrxR1 and ROS modulation.
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