p53-independent apoptosis induced by genistein in lung cancer cells

Lung cancer is the leading cause of cancer-related deaths in the world, wit h increasing incidence in many developed countries. Epidemiological data su ggest that consumption of soy products may be associated with a decreased r isk of cancer. Despite the association of nutrition and cancer, the molecul ar mechanisms by which the active metabolite in the soy diet, genistein, ex erts its biological response have not been studied. We previously showed th at genistein can inhibit the growth of H460 nan-small-cell lung cancer (NSC LC) cells in vitro. To explore the molecular mechanisms by which genistein inhibits the growth of NSCLC cells, we investigated cell growth inhibition, modulation in gene expression, and induction of apoptosis by genistein in H460 cells, which harbor wild-type p53, and H322 cells, which possess mutat ed p53. Genistein was found to inhibit H460 and H322 cell growth in a dose- dependent manner. Staining with 4,6-diamidino-2-phenylindole, poly(ADP-ribo se) polymerase cleavage, and flow cytometric apoptosis analysis were used t o investigate apoptotic cell death, and the results show that 30 mu M genis tein causes cell death via a typical apoptotic pathway. Western blot analys is demonstrated upregulations of p21(WAF1) and Bax by genistein in wild-typ e and mutant p53 cell lines. Furthermore, cells treated with genistein show ed an increased expression of endogenous wild-type p53, while the level of the mutant p53 protein remained unchanged. From these results, we conclude that genistein induces apoptosis in NSCLC cells through a p53-independent p athway and, thus, may act as an anticancer agent.