الفهرس 
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Abstract
This study was designed firstly to evaluate chemopreventive and therapeutic effect of capsaicin employing a two-stage model of rat liver carcinogenesis. Also,induction of apoptosis through cytochrome c activation. Secondly to explore the mechanism underlying capsaicin-induced cell death in human HepG2 cancer cells. Also, effect of treatment of HepG2 cells with capsaicin on their proliferation/ viability, halts cell cycle progression, and induction of apoptosis through increasing PARP-1 cleavage and induce cell cycle arrest by decreasing the expression of cyclin D1.
Results of in vivo study revealed that administration of DENA and PB caused significant elevation in serum (ALT, AST, and ALP) activities, MDA and NO levels, it significantly decreased ALB and cytochrome c level. Also, it depleted the antioxidant activities of GSH and GST. In preventive group treatment with capsaicin restored the levels of liver markers near to normal, significantly decreased MDA level and increased NO level thereby confirming hepatoprotective effect by increasing oxidative stress and induced apoptosis by significant increase of cytochrome c level. While, in therapeutic group capsaicin decreased NO and MDA levels and increased GSH and GST activities. A section of liver was also subjected to histopathological analysis that confirmed our results. In vitro study declared that treatment of HepG2 cells with Capsaicin resulted in decreased the percentage of viable cells in a dose-dependent manner, dramatic morphological changes in HepG2 cell line after 24 h, internucleosomal degradation of DNA resulting in ladder-shaped nucleosomal DNA fragments. Also, Capsaicin induces apoptosis in HepG2 cells and this response was associated with activation of caspase-3, decreased the expression of cyclin D1 and PARP-1 as evident by their cleavage.
Conclusion: In therapeutic group capsaicin acts by decreasing oxidative stress induced by DENA and PB, while in preventive group acts by increasing oxidative stress and reducing antioxidant activity. Also, Capsaicin induces apoptosis in HepG2 cells and this response is associated with mitochondrial pathways, which further activates caspase-3 and PARP as evident by their cleavage. The apoptosis may be mediated via a cell cycle arrest at the G1/S phase.