The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial
Yan-Yan Yan1, Jian-Ping Bai, Yong Xie
1Institute of Brain Science, Shanxi Datong University, Datong, Shanxi 037009, P.R. China.
Abstract:
It has become evident that some of the natural or synthetic triterpenoids are natural proteasome inhibitors that have great potential for use in cancer prevention and treatment. However, the mechanisms for the antitumor activity of triterpenoids remain to be elucidated. In the present study, we investigated the anticancer activities of a natural triterpenoid, pristimerin, and the signaling pathways affected. Pristimerin was found to possess potent cytotoxic effects, inducing apoptosis and inhibiting proliferation in U87 human glioma cells. Hoechst 33258 staining and Annexin V/PI double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. Moreover, western blotting assay revealed that this apoptotic induction was associated with activated caspase-9, caspase-3, PARP cleavage and downregulation of Bcl-xl/Bax in a concentration-dependent manner. Pristimerin also increased the generation of reactive oxygen species and induced the subsequent release of cytochrome c from the mitochondria into the cytosol. Additionally, pristimerin downregulated EGFR protein expression and inhibited downstream signaling pathways in U87 cells. Our results suggest that pristimerin may have potential as a new targeting therapeutic strategy in the treatment of EGFR-overexpressing gliomas.
Insights
Pristimerin, a natural compound, shows potent anticancer effects by inducing apoptosis and inhibiting proliferation in human glioma cells. It targets key signaling pathways, including EGFR, offering potential for targeted cancer therapy.
Area of Science:
- Natural Products Chemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Triterpenoids are recognized for their potential as cancer chemopreventive and therapeutic agents.
- The precise mechanisms underlying the antitumor activity of triterpenoids require further elucidation.
- Understanding these mechanisms is crucial for developing novel cancer treatments.
Purpose of the Study:
- To investigate the anticancer activities of the natural triterpenoid pristimerin.
- To identify the specific signaling pathways modulated by pristimerin in cancer cells.
- To evaluate pristimerin's potential as a therapeutic agent for EGFR-overexpressing gliomas.
Main Methods:
- Cytotoxicity assays and apoptosis detection (Hoechst 33258, Annexin V/PI staining) in U87 human glioma cells.
- Western blotting to analyze apoptosis-related proteins (caspases, PARP, Bcl-xl/Bax) and EGFR signaling.
- Measurement of reactive oxygen species (ROS) generation and mitochondrial cytochrome c release.
Main Results:
- Pristimerin exhibited potent dose-dependent cytotoxic effects, inducing apoptosis and inhibiting proliferation in U87 glioma cells.
- Apoptosis induction was linked to caspase activation, PARP cleavage, altered Bcl-xl/Bax ratio, ROS generation, and cytochrome c release.
- Pristimerin downregulated EGFR protein expression and inhibited its downstream signaling pathways.
Conclusions:
- Pristimerin demonstrates significant anticancer properties against human glioma cells through multiple molecular mechanisms.
- The compound effectively induces apoptosis and inhibits proliferation by targeting key cellular pathways.
- Pristimerin shows promise as a potential therapeutic strategy for EGFR-overexpressing gliomas.
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