Effects And Mechanism Of Apoptosis Induced By Oleanolic Acid Derivatives In HepG2 Cells And Hep3B Cells

At present,with the increasing incidence and mortality of cancer,cancer has become a serious threat to human life and social development of major diseases.About 8.8 million people worldwide die of cancer each year,accounting for about one-sixth of the world's total annual death,according to World Health Organization figures.China is a large cancer country,the incidence of cancer accounted for about22%of the world,cancer deaths accounted for about 27%of the world,and as the population aging trend and disease patterns change,cancer burden is more and more heavy,cancer prevention and treatment is facing severe situation.Medical treatment is an important means of cancer treatment,and screening the anticancer drugs with high efficiency and low toxicity from the natural products has become the main means.Pentacyclic triterpenes have contributed to the study on modern therapeutic drugs.Oleanolic acid?OA?is a pentacyclic triterpenoid with broad-spectrum anticancer activity,but its water solubility is poor and its biological activity is weak.So many scholars have synthesized its structure to obtain the highly efficient and low toxicity compounds.In this study,we studied the anticancer activity of three new synthetic oleanolic acid derivatives,and we studied the anticancer effect and the mechanism of OA-Bn-5-2-S in HepG2 cells and Hep3B cells.The toxicity of OA-Bn-5-2-S in HepG2 cells,Hep3B cells and L02 cells was determined by the MTT assay.The results showed that the IC₅₀ were valued4.78±1.44?M,13.23±4.76?M and 23.43±0.91?M,respectively.Marked morphological changes of HepG2 cells and Hep3B cells can be observed under the microscope after OA-Bn-5-2-S treated,while that of L02 cells don't.The results of Hochest 33342 staining,DNA ladder detection and flow cytometry showed that OA-Bn-5-2-S induced HepG2 cells and Hep3B cells apoptosis and inhibited the growth of HepG2 cells and Hep3B cells,it also blocked the HepG2 cells cycle in G0/G1 phase.The effects of OA-Bn-5-2-S on the mitochondrial membrane potential and the activity of Caspase-3 and Caspase-9 in HepG2 cells were further studied by Western blot.It was further deduced that OA-Bn-5-2-S could promote the expression of Caspase-3 and Caspase-9 protein and decrease the mitochondrial membrane potential to activate mitochondrial pathway and then induce HepG2 cells apoptosis;but Hep3B cells didn't.The work provides the experimental basis for the structural optimization of oleanolic acid derivatives,and provides important theoretical value for the development of new anticancer lead compounds with high efficiency and low toxicity.