Effect of isoflavones on oral squamous cell carcinoma cell lines.

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High morbidity and mortality associated with oral squamous cell carcinoma (OSCC) are largely due to late stage diagnosis. Despite significant advances in therapeutic strategies, the five-year survival rate for oral cancer remains at about fifty percent. A chemopreventive approach may be an effective alternative or adjunct to current therapies. Previous studies have shown anti-tumor effects of soy isoflavones in several cancers, including oral cancer. However, their mechanisms of action are still unclear. We hypothesized that soy isoflavones may inhibit multiple signaling pathways implicated in oral carcinogenesis. Our aim was to investigate the in vitro effects of three isoflavone derivatives, genistein, biochanin A, and daidzein, on SCC15 and SCC25 squamous cell carcinoma cell lines. In cell proliferation experiments, using MTT assays, we found that genistein, biochanin A, and daidzein inhibited SCC15 and SCC25 cell growth with an IC50 of 42μM, 48μM, and 67μM, respectively. We investigated the effect of isoflavones on ERK and AKT pathways. Our results, from western blot analysis, suggest that both genistein and biochanin A induced decreases in phosphorylation of ERK and AKT at 50μM and 100μM concentrations. Taken together, our results clearly demonstrate a differential regulation of oncogenic pathways by various soy isoflavones in OSCC cell lines. Thus, in vitro tumor progression models can be utilized to study the preventive and therapeutic roles of soy isoflavones in OSCC. (Our work was supported, in part, the University Research Committee, ISU, grant #FY2002-09 and NIH/NCRR INBRE, grant #P20RR16454.)