Effect And Mechanism Of Synthetic Flavonoids Against Human Lung Cancer Cells

Lung cancer is difficult to diagnose early and is the leading cause of cancer death worldwide.About 300,000 people are diagnosed with lung cancer each year in China,and about 250,000 die from the disease.Despite major advances in current diagnosis and treatment of lung cancer,the prognosis remains poor,with a five-year average survival rate of about 16 percent.Therefore,it is urgent to develop new anti-lung cancer drugs with higher sensitivity and fewer side effects.Flavonoids have a broad spectrum of pharmacological activities and a wide range of biological effects,including anti-cancer,anti-inflammatory,anti-oxidant,anti-mutagenic,anti-fungal,anti-allergic and anti-viral activities.?Thiophen-2-group?-4H-chromene-3-group sulfonate?JLS-6??thiophen-2-group?-4H-chromene-2-group sulfonate?JLS-7?are two new synthetic flavonoids with small molecular structure.The basic structure of 3-flavonoids is further modified to investigate whether it can inhibit tumor cell proliferation,especially for study on the proliferation inhibition and mechanism of A549 cells.The purpose of this paper was to explore the mechanism of apoptosis induced by JLS-6 and JLS-7 in A549 cells by MTT colorimetry,flow cytometry,DAPI staining,Casapse-3,-8,-9 activity assay,mitochondrial membrane potential assay and western blot.The MTT colorimetric method was used to detect other types of cancer cells at the same time.It can be preliminarily judged that JLS-6 and JLS-7 also have a proliferation inhibitory effect on some tumor cells,but the most significant proliferation inhibitory effect is on A549 cells.The IC₅₀ values?half inhibitory concentrations?of JLS-6 and JLS-7 were 5.87?g/mL and 7.69?g/mL,respectively.After acting on A549 cells,JLS-6 and JLS-7 will transmit apoptotic signals,causing Bax and Bak to translocate to mitochondria and thus change the permeability of the outer membrane of mitochondria,causing mitochondria to release Cyto.c?cytochrome c?to activate Caspase-9 and eventually start endogenous apoptotic pathway.To sum up,JLS-6 and JLS-7 promote the apoptosis of A549 cells by initiating endogenous apoptotic pathways.In addition,it is worth noting that the expression of c-IAP2 in the anti-apoptotic protein IAPs family significantly decreased with time after JLS-6 and JLS-7 treatment of cells,while the expression of Bcl-2,Bcl-xL,c-IAP1 and X-IAP proteins remained unchanged.