Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

In the 21st century, cancer is considered a major cause of death, specifically liver cancer hepatocellular carcinoma (HCC), which is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018. Sorafenib (SF) was recommended as the first-line treatment for advanced HCC as it is a small molecule target therapy but although it is an attractive and approved treatment for HCC but still needs researches to avoid its side effects. Therefore, the present study was constructed in order to explore the potential anti-cancer activity of a novel combination of plant-derived natural products consisting of thymoquinone (TQ) and Ellagic acid (EA) against HCC on Hep-G2 cells, comparing their effects to a standard drug SF and investigating any synergism between each of them and SF, in addition to investigating the underlying mechanisms for such modulation with emphasis on proliferation and apoptosis. The effect of SF, TQ, and EA were evaluated separately and in combination on HepG2. Cell viability, MAPK, AKT, GPC-3, and GSK3Ý activities. Moreover; PSTAT-3, VEGF, MMP-9, caspase-3, and Bcl2/BAX ratio, as well as NF-mB, TNF-Ü, and IL-6 were measured. Thymoquinone and ellagic acid combination showed significant cell inhibition, affecting all indicators of cell proliferation and angiogenesis in results near to SF results, in the same way, the addition of EA to SF increased its effectiveness. All these results give promising combinations to increase the effectiveness and by default decrease the side effects of SF or use TQ and EA combination instead of SF alone

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