growth and proliferation signal cascades. Inhibition of DNA topoisomerase II also plays an important role in the cytotoxic activity of genistein. The observation that transition of normal lymphocytes from quiescence (G0) to the G1 phase of the cell cycle is particularly sensitive to genistein prompted the authors to suggest that this isoflavone may be potential immunosuppressant. Genistein has been used to selectively target pre B-cells via conjugation with an anti-CD19 antibody. Studies on rodents have found genistein to be useful in the treatment of leukemia, and that it can be used in combination with certain other antileukemic drugs to improve their efficacy. Estrogen receptor — more cancer links Due to its structure similarity to 17β-estradiol (estrogen), genistein can compete with it and bind to estrogen receptors. However, genistein shows much higher affinity toward estrogen receptor β than toward estrogen receptor α. Data from in vitro and in vivo research confirms that genistein can increase rate of growth of some ER expressing breast cancers. Genistein was found to increase the rate of proliferation of estrogen-dependent breast cancer when not cotreated with an estrogen antagonist. It was also found to decrease efficiency of tamoxifen and letrozole - drugs commonly used in breast cancer therapy. Genistein was found to inhibit immune response towards cancer cells allowing their survival. Effects in males Isoflavones can act like estrogen, stimulating development and maintenance of female characteristics, or they can block cells from using cousins of estrogen. In vitro studies have shown genistein to induce apoptosis of testicular cells at certain levels, thus raising concerns about effects it could have on male fertility; however, one study found that isoflavones had "no observable effect on endocrine measurements, testicular volume or semen parameters over the study period." in healthy males given isoflavone supplements daily over a 2-month period. Carcinogenic and toxic potential Genistein was, among other flavonoids, found to be a strong topoisomerase inhibitor, similarly to some chemotherapeutic anticancer drugs ex. etoposide and doxorubicin. In high doses it was found to be strongly toxic to normal cells. This effect may be responsible for both anticarcinogenic and carcinogenic potential of the substance. It was found to deteriorate DNA of cultured blood stem cells, which may lead to leukemia. Genistein among other flavonoids is suspected to increase risk of infant leukemia when consumed during pregnancy. Sanfilippo syndrome treatment Genistein decreases pathological accumulation of glycosaminoglycans in Sanfilippo syndrome. In vitro animal studies