http://dx.doi.org/10.4314/tjpr.v11i1.7
Abstract
Purpose:
To evaluate in vitro (using human hepatoma HepG2 cells)
and in vivo (using mouse liver with diethlynitrosamine
(DEN)-induced hepatocarcinogenesis) effect of a
standardized decoction on the expression of p53 (tumour
suppressor) and p21 (cyclin kinase inhibitor) genes with
the long-term goal of developing the formulation into a
globally acceptable therapy for hepatocellular carcinoma
(HCC).
Methods:
The effect of the decoction on (a) mRNA and (b) protein
expression of p53 and p21 genes in HepG2 cells and mouse
livers with DEN-induced early hepatocarcinogenesis were
evaluated by (a) reverse transcription PCR (RT-PCR) and
(b) immunohistochemical and Western blot analysis,
respectively.
Results:
The results demonstrated that the decoction
significantly (p < 0.001) enhanced the expression of p53
and p21 genes in a time- and dose-dependent manner in
HepG2 cells. A dose of 75 µg/ml significantly increased
p53 mRNA at 24 and 48 h and p21 mRNA at 12, 24, 48 h of
incubation with the decoction (p < 0.01). Induction of
hepatocarcinogenesis in mice significantly increased
hepatic expression of both p53 and p21 compared to
distilled water control (p < 0.001), while treatment
with the decoction further enhanced expression of both
genes in DEN-induced hepatocarcinogenesis (p < 0.01).
Conclusion:
Overall, the findings demonstrate that the decoction may
mediate its reported antihepatocarcinogenic effect, at
least in part, through the modulating activities of
genes involved in tumour suppression and cell cycle
arrest.
Keywords:
Hemidesmus indicus,
Nigella sativa, Smilax glabra, HepG2 cells,
Diethylnitrosamine, p53, p21.
