الفهرس 
Materials and methodsOnly 14 pages are availabe for public view
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Abstract
(-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has shown excellent effects in preventing and treating, many cancers including hepatocellular carcinoma (HCC) in preclinical model systems. Despite of the promising results in preclinical settings, EGCG applicability in vivo has been hampered largely due to inefficient bioavailability. We employed the use of nanotechnology to improve the outcome of anticancer effect. The present study investigated the antitumor activity of EGCG encapsulated into chitosan nanoparticles (CSNPs) in in Hepg2 cells in vitro. This study reports the synthesis, characterization of a formulation of chitosan encapsulating EGCG (Chit-nanoEGCG) for treatment of HCC in vitro. Chit-nanoEGCG caused dose-dependent loss of cell viability. Chit-nanoEGCG treatment induced a significant up-regulation of both P53 and Bax and down-regulation of Bcl-2 genes expression compared to that of native EGCG treatment and cisplatin treatment in HepG2 cells. The present results demonstrated marked induction of CD95, caspase-9, caspase-3 and PARP apoptotic genes expression in HepG2 cells by chit-nanoEGCG treatment. In addition, chit-nanoEGCG treatment induced a significant down-regulation of BMI1, Ezrin, OCT4, SOX2, NANOG, NOTCH1, ABCG2, CD44, and CD133 cancer stem cells genes compared to that of native EGCG treatment, cisplatin treatment, and control group in HepG2 cells. Moreover, the current study shows that chit-nanoEGCG treatment significantly down-regulated the expression of the mTOR, PI3K, RALA, and c-MET signaling pathway genes when compared with native EGCG treatment and cisplatin treatment in HepG2 cells. In conclusion, the present results suggest that chit-nanoEGCG inhibits tumor growth and progression of HepG2 cells, through induction of apoptosis and regulation of multiple cancer-related signaling pathways. Encapsulation of EGCG into chitosan nanoparticles provided a good platform for cancer chemotherapy and raised existing application of different polyphenols for nanochemotherapy.