Inhibition Of Cell Growth And Proliferation By Genistein And Isoprunetin In Human PC-9Lung Cancer And U87-MG Glioblastoma Cells

Cancer is a growing health problem around the world, and it has been estimated thatabout40%of human cancers could be prevented through appropriate lifestylemodification. Epidemiologically, the incidence and mortality of many kinds of cancer,such as breast and prostate that are considered hormone related, appear to be significantlylower in Asian countries than in the USA and European countries. Numerous studies haveshown that the consumption of foods rich in soy isoflavones may be associated with areduction in the risk of these cancers. Some studies found an inverse association betweenisoflavone intake and risk of lung cancer in never smokers. Genistein, the predominantisoflavone in soybean, has strongly been suggested as an agent with some putativeantitumor effects. Isoprunetin is another isoflavone which shares similar structure andantitumor effects with genistein.To study the role of isoflavone on inhibitory effects against cancer cells, PC-9humanlung cancer cells and U87-MG human glioblastoma cells were treated with genistein andisoprunetin. The results showed that treatment of PC-9cells with25μM genistein for48hours significantly inhibited cell growth, while isoprunetin could have weaker inhibitoryactivity. A similar nonsignificant inhibition of cell growth was seen in U87-MG cells.Although the inhibition of cell growth in U87-MG cells was nonsignificant, the inhibitionof cell proliferation in PC-9and U87-MG cells by genistein and isoprunetin was showedto be significant. The results of Western Blotting showed that treatments of PC-9andU87-MG cells with genistein and isoprunetin attenuated the levels of p-Akt and p-GSK3β,but inhibition of GSK3with LiCl could further inhibited cell growth and proliferation.The results demonstrated that inhibition of cell growth and proliferation by genistein andisoprunetin was independent on GSK3. The results of RNA interfere by p110α or p110βsiRNA in U87-MG cells showed that p110α or p110β was not involved in the decrease ofp-Akt and p-GSK3β, therefore the inhibitory effects of cell growth and proliferation bygenistein and isoprunetin were independent on p110α/β. Pretreated with ascorbic acidcouldn’t rescue the inhibitory effects of cell growth and proliferation by genistein andisoprunetin, so inhibition of cell growth and proliferation by genistein and isoprunetin was independent on anti-oxidantive activity. Therefore, treatment of PC-9cells with100μMgenistein for48hours significantly activated Caspase-3, which demonstrated thatgenistein induced apoptosis in PC-9cells.In the present study, we demonstrated that genistein and isoprunetin inhibited cellgrowth and proliferation in PC-9human lung cancer cells and U87-MG humanglioblastoma cells and the inhibitory effects of cell growth and proliferation wereindependent on GSK3, p110α/β and anti-oxidantive activity. These results stronglysuggest that isoflavone genistein and isoprunetin are potential preventive and therapeuticagents in PC-9human lung cancer cells and U87-MG human glioblastoma cells.