Genistein is an
isoflavone found in soy, and its chemo-preventive and -
therapeutic effects have been well established from in vitro studies. Recently, however, its therapeutic actions in vivo have been questioned due to contradictory reports from animal studies, which rely on rodent models or implantation of cell lines into animals. To clarify in vivo effects of
genistein in advanced
prostate cancer patients, we developed a patient-derived
prostate cancer xenograft model, in which a clinical
prostatectomy sample was grafted into immune deficient mice. Our results showed an increased lymph node (LN) and secondary organ
metastases in
genistein-treated mice compared to untreated controls. Interestingly, invasive malignant cells aggregated to form islands/
micrometastasis only in the secondary organs of the
genistein-treated groups, not in the untreated control group. To understand the underlying mechanism for metastatic progression, we examined cell proliferation and apoptosis on
paraffin-sections. Immunohistological data show that
tumors of
genistein-treated groups have more proliferating and fewer apoptotic
cancer cells than those of the untreated group. Our immunoblotting data suggest that increased proliferation and
metastasis are linked to enhanced activities of
tyrosine kinases, EGFR and its downstream Src, in
genistein-treated groups. Despite the chemopreventive effects proposed by earlier in vitro studies, the
cancer promoting effect of
genistein observed here suggests the need for careful selection of patients and safer planning of clinical trials.