The Mechanism Of Human Liver Cancer HepG2 Cells Apoptosis Induced By Synthetic Flavonoids JLS-6 And JLS-7

Cancer,a complex disease caused by activation of oncogenes or mutation of tumor suppressor genes,among which liver cancer is one of the most common primary malignant tumors and a major malignant disease that endangers human health.Most liver cancers are diagnosed in the middle and late stages and cannot be treated with surgery,and there is no effective treatment.Therefore,it is urgent to develop a drug for the treatment of liver cancer with good curative effect and low side effects.Flavonoids have a variety of pharmacological effects,of which some progress has been made in anti-tumor.However,due to the low content of natural flavonoids,the activity is not ideal.Therefore,the use of chemical synthesis to synthesize new flavonoids may be an important way to develop anti-tumor drugs.JLS-6??Thien-2-yl?-4H-benzopyran-3-yl 3-methylbenzenesulfonate?and JLS-7??Thien-2-yl?-4H-benzopyran-3-yl 2-methylbenzenesulfonate?selected in this study are two synthetic flavonoids,and we will explore their anti-tumor effects.The MTT test results confirmed that JLS-6 and JLS-7 have a certain proliferation inhibitory effect on 11 tumor cells,among which the inhibition on human liver cancer HepG2cells,human esophageal cancer KYSE510 cells,and prostate cancer PC-3M cells is very obvious.Among them,the half inhibitory concentration of JLS-6 on these three tumor cells,that is,the IC₅₀0 values were 5.6?g/mL,1.4?g/mL,and 13.7?g/mL,respectively,and the IC₅₀0 values of JLS-7 on these three tumor cells were 7.1?g/mL,7.8?g/mL,7.7?g/mL;The inhibitory effect on the other 8 types of tumor cells is weak,with IC50 values between 15-50?g/mL.The purpose of this study was to investigate in depth the mechanism by which JLS-6 and JLS-7 inhibit the proliferation of human liver cancer HepG2 cells.First,through the observation of cell morphology,the number of apoptosis statistics,the determination of Caspase enzyme activity and the results of PARP fragmentation,it is concluded that JLS-6 and JLS-7 can achieve proliferation inhibition by inducing apoptosis of human liver cancer HepG2cells.Secondly,Caspase-8 and-9 enzyme activity measurements and their cleavage results confirmed that JLS-6 and JLS-7 can initiate mitochondrial-mediated endogenous apoptosis.Immunoblotting experiments confirmed that when JLS-6 and JLS-7 act on the cells,Bax and Bak in the cells are translocated to the mitochondrial membrane to form pores,and Cyto.c and Smac in the mitochondria are released into the cytoplasm.Cyto.c can bind to Apaf-1,leading to the activation of Caspase-9.Finally,immunoblotting analysis to detect the expression of anti-apoptotic protein proved that the degradation of XIAP and BcL-xL promoted the apoptosis induced by JLS-6 and JLS-7,respectively.In summary,the results show that JLS-6and JLS-7 have an inhibitory effect on the proliferation of various tumor cells,and the most obvious inhibitory effect on human liver cancer HepG2 cells is achieved by inducing mitochondrial-mediated endogenous apoptosis.