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Published on: January 18, 2017
Nuclear factor-kappa B as a promising target for selenium chemoprevention in rat hepatocarcinogenesis
Nasar Y Alwahaibi1, Siti B Budin, Jamaludin Mohamed
1Department of Biomedical Sciences, Faculty of Allied Health Sciences, National University of Malaysia, Julan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia. nasarsidab@yahoo.com
Background And Aims:
Selenium's molecular mechanism for cancer chemoprevention remains unknown. We aimed to study the gene expression of nuclear factor-kappaB (NF-kappaB), tumor growth factor-alpha (TGF-alpha) and cyclin D1 and the effects of sodium selenite using preventive and therapeutic approaches in chemically-induced hepatocarcinogenesis in rats.
Methods:
Rats were divided randomly into six groups: negative control, positive control (diethyl nitrosamine [DEN] + 2-acetylaminofluorene [2-AAF]), preventive group, preventive control (respective control for preventive group), therapeutic group and therapeutic control (respective control for therapeutic group). The relative gene expression of NF-kappaB, TGF-alpha and cyclin D1 in liver tissues were measured using real-time polymerase chain reaction.
Results:
The findings showed that the gene expression of NF-kappaB in the preventive group and its respective control was significantly lower (P < 0.05) when compared with both the negative and positive controls. However, the expression of NF-kappaB in the positive controls and therapeutic group was significantly higher (P < 0.05) when compared with the negative controls. The expression of TGF-alpha and cyclin D1 was insignificant in all groups.
Conclusion:
The inhibition of the NF-kappaB pathway in the initiation phase of hepatocarcinogenesis could be a promising target for selenium chemoprevention. However, further studies are required.
Insights
Sodium selenite may prevent liver cancer by inhibiting the nuclear factor-kappaB (NF-kappaB) pathway during cancer initiation. Further research is needed to confirm these findings in selenium chemoprevention strategies.
Area of Science:
- Hepatocarcinogenesis research
- Molecular mechanisms of cancer chemoprevention
- Nutritional biochemistry and cancer
Background:
- The precise molecular mechanisms underlying selenium's cancer chemoprevention are not fully understood.
- Investigating the role of key signaling pathways and gene expression in chemically induced liver cancer is crucial.
Purpose of the Study:
- To investigate the effects of sodium selenite on the gene expression of nuclear factor-kappaB (NF-kappaB), tumor growth factor-alpha (TGF-alpha), and cyclin D1.
- To explore the preventive and therapeutic potential of sodium selenite in a rat model of chemically induced hepatocarcinogenesis.
Main Methods:
- Rats were assigned to six groups, including negative control, positive control (DEN + 2-AAF), and groups for preventive and therapeutic sodium selenite administration.
- Real-time polymerase chain reaction was employed to quantify the relative gene expression of NF-kappaB, TGF-alpha, and cyclin D1 in liver tissues.
Main Results:
- Sodium selenite significantly reduced NF-kappaB gene expression in the preventive group compared to controls (P < 0.05).
- NF-kappaB expression was elevated in positive controls and the therapeutic group versus negative controls.
- No significant differences in TGF-alpha and cyclin D1 gene expression were observed across all experimental groups.
Conclusions:
- Inhibition of the NF-kappaB pathway during the initiation phase of hepatocarcinogenesis represents a potential mechanism for selenium chemoprevention.
- Further investigations are warranted to fully elucidate selenium's role in cancer prevention and its molecular targets.
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