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WITHDRAWN: Selenite induces apoptosis in colorectal cancer cells through interaction with thioredoxin reductase
Fang Huang, Jing Huang, Qing Lv
1The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China caiminxu@yahoo.com.cn.
Abstract:
Ahead of Print article withdrawn by publisher. The chemopreventive and chemotherapeutic effects of selenium compounds has been well validated in colorectal cancer by epidemiologic and pre-clinical studies, but the underlying mechanisms still remains elusive. We provide evidence that interaction between selenium metabolites and selenoproteins participates in colorectal cancer suppression induced by selenite. We found that supranutritional doses of selenite could induces inhibition of thioredoxin system and apoptosis in SW480 cells, and cause direct modifications of thiol groups on TrxR protein. Moreover, we showed that TrxR ablation sensitized apoptosis induced by selenite, and the synergistic effect was related to Bax activation and mitochondrial apoptotic pathway. Our results proposed that TrxR is an important target for selenite in colorectal cancer suppression, and selenite in combination with TrxR inhibition could be an effective strategy to treat colorectal cancer.
Insights
Selenium compounds, like selenite, show promise in colorectal cancer treatment by targeting the thioredoxin system. Selenite combined with thioredoxin reductase inhibition enhances cancer cell apoptosis, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Epidemiologic and preclinical studies validate selenium compounds' chemopreventive and chemotherapeutic effects in colorectal cancer.
- The precise mechanisms underlying selenium's action in colorectal cancer remain largely unknown.
Purpose of the Study:
- To investigate the interaction between selenium metabolites and selenoproteins in colorectal cancer suppression.
- To elucidate the role of thioredoxin reductase (TrxR) as a target for selenite in colorectal cancer.
Main Methods:
- Treatment of SW480 colorectal cancer cells with supranutritional doses of selenite.
- Analysis of thioredoxin system inhibition and apoptosis induction.
- Investigation of direct modifications on TrxR protein.
- Assessment of TrxR ablation effects on selenite-induced apoptosis and the mitochondrial pathway.
Main Results:
- Selenite inhibited the thioredoxin system and induced apoptosis in SW480 cells.
- Selenite directly modified thiol groups on the TrxR protein.
- TrxR ablation sensitized cells to selenite-induced apoptosis, involving Bax activation and the mitochondrial pathway.
Conclusions:
- Thioredoxin reductase (TrxR) is identified as a key target for selenite in colorectal cancer suppression.
- Combining selenite with TrxR inhibition presents a promising therapeutic strategy for colorectal cancer treatment.
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