Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract

Seven isoflavones, biochanin A, daidzein, genistein, genistin, prunectin, puerarin, and pseudobaptigenin were tested for cytostatic and cytotoxic effects on 10 newly established cancer cell lines of the human gastrointestinal origin. Proliferation of HSC-41E6, HSC-45M2, and SH101-P4 stomach cancer cell lines was strongly inhibited by biochanin A and genistein, whereas other stomach, esophageal, and colon cancer lines were moderately suppressed by both compounds. Biochanin A and genistein were cytostatic at low concentrations (< 20 micrograms/ml for biochanin A, < 10 micrograms/ml for genistein) and were cytotoxic at higher concentrations (> 40 micrograms/ml for biochanin A, > 20 micrograms/ml for genistein). DNA fragmentation was observed at cytotoxic doses of both compounds, indicating the apoptotic mode of cell death by the compounds. Chromatin condensation and nuclear fragmentation of each cell line were also observed. The advent of apoptosis was dose dependent for both isoflavones. Biochanin A suppressed tumor growth of HSC-45M2 and HSC-41E6 lines in athymic nude mice. Our results suggest that two of isoflavone derivatives, biochanin A and genistein, inhibit the cell growth of stomach cancer cell lines in vitro through activation of a signal transduction pathway for apoptosis. Moreover, in vivo experiments demonstrate that biochanin A can be used as an anticancer agent.