Nuclear factor-kappa B as a promising target for selenium chemoprevention in rat hepatocarcinogenesis.
OBJECTIVE
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.


CONCLUSIONS
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.
Alwahaibi
Nasar Y
NY
Department of Biomedical Sciences, Faculty of Allied Health Sciences, National University of Malaysia, Julan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia. nasarsidab@yahoo.com
Budin
Siti B
SB
Mohamed
Jamaludin
J
Alhamdani
Aisha
A
D015073:2-Acetylaminofluorene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics; D004052:Diethylnitrosamine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018038:Sodium Selenite / Q000494:pharmacology*; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics
D016588:Anticarcinogenic Agents; C530106:Ccnd1 protein, rat; D016328:NF-kappa B; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D019938:Cyclin D1; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D018038:Sodium Selenite