7P - Selenium-enriched polysacchride green tea extract alters the early stage hepatocellular carcinoma by angiogenesis hypoxia and metastatic inhibition
|Date||17 December 2016|
|Event||ESMO Asia 2016 Congress|
|Topics|| Basic Science
|Citation||Annals of Oncology (2016) 27 (suppl_9): ix1-ix8. 10.1093/annonc/mdw573|
V. Kumar1, P.C. Bhatt2, F. Anwar3, A. Verma1
Targeting various pathways during progression and expansion of hepatocellular carcinoma (HCC) is one promising strategy to control the complications of liver cancer. The present investigation targeted the potential effect of selenium-enriched green tea polysaccharides on HOX, hypoxia-induced factor, Vascular Endothelium Growth Factor (VEGF), matrix metalloproteinase (MMP-2 and MMP-9), alpha fetoprotein (ALF) and CD31 in diethylnitrosamine induced HCC rats.
The extract was rich in uronic acid (3.2%), carbohydrate (91.2%) and 4.5 μg/g of selenium to represent SCP. This extract was evaluated for apoptosis mechanism against HCC cell lines viz., Hep-G2 and HuH-7. Invivo study, can be read as: Normal; NC + SCP (20 mg/kg); DEN treated; DEN + SCP (20 mg/kg). The treatment was initiated a week before the DEN administration and was carried for 22 weeks. HCC via DEN is known for significant alteration in biochemical, inflammatory, antioxidant parameters and liver histopathology. Furthermore we also estimated the HOX, HIF, VEGF, MMP-2 and MMP-9, ALF and CD31 parameters.
In vitro studies confirmed the inhibition of the growth of Hep-G2 and HuH-7 cells in a dose-dependent manner via scavenging the cell at G2 phase of cells. Cell death was confirmed via enhanced caspase 3, 9 activity and Bax/Bcl2 ratio, suggesting the effect on the c-caspase pathway on apoptosis. The animal studies confirm the alteration in biochemical, antioxidant and inflammatory markers. Further to substantiate our claim SCP also inhibited the protein elevation of HIF-1a, VEGF, MMP-2, 9 and CD31 compared with DEN control group rats. The alteration in these parameters was sufficient to confirm the reduction of angiogenesis, hypoxia and metastasis and proved the potential effect of SCP at early expansion stage of disease.
Collectively, we can conclude that selenium-enriched polysaccharides of green tea reduced the progression and expansion of hepatocellular carcinoma via multiple mechanisms.
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All authors have declared no conflicts of interest.