HCC is the sixth commonest cancer worldwide and the third one to cause death. In Egypt, liver cancer forms 1.68% of total malignancies. HCC constitutes 70.48% of liver tumors. HCC represents the main complication of cirrhosis. Chemotherapy has an undesirable side effect, so the drugs are used instead. Bee venom and curcumin have been used as folk medicine since ancient times. This study examined the anticancer potential of bee (Apis mellifera) venom and curcumin compared with a synthetic anticancer of Doxorubicin (Dox) drug, and tested the effect of combination between the tested three components to decrease the chemotherapy side effect. Cytotoxicity activity of Bee venom and curcumin were determined using MTT assay. Cell cycle was determined by flow cytometry and apoptotic detection by using Annexin V-FITC Assay. RNA was extracted to evaluate the expression of P53, Bcl2 & NF-κB genes using semi-quantitative RT-PCR after 24hrs. HepG2 cell line was more save to test bee venom and curcumin onHepG2 cell line. Curcumin and bee venom had IC50 as 15.15 & 31μg/ml with HepG2 cell line. Combination between Bee venom, curcumin, and doxorubicin drug had apoptotic effect against HepG2cell line through the elevation by increasing the level of p53 & NF-κB genes and decrease
the Bcl-2 gene expression.