Genistein Increases Epidermal Growth Factor Receptor Signaling and Promotes Tumor Progression in Advanced Human Prostate Cancer

Abstract

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.

Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

“…Although the initial impetus for these studies related to the treatment of accidentally exposed individuals, genistein is also of interest therapeutically for cancer patients. It has been reported to inhibit invasion, metastasis and angiogenesis in vitro and in vivo in a number of cancers, including breast cancer, although recent data have questioned its effect in prostate cancers (49–57). A recent pilot study has reported that treatment with an isoflavone cocktail including genistein can reduce side effects after radiation treatment of prostate cancer (58).…”

Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons

“…There is a wealth of literature with respect to the effects of isoflavones on EGFR signaling. Importantly, the most prevalent isoflavone in soy is genistein, which can reduce EGF-mediated DNA synthesis (163), decrease EGFR levels (164, 165), decrease or increase phosphorylation of EGFR (166, 167), and transactivate EGFR (168). …”

A multi-targeted approach to suppress tumor-promoting inflammation

“…A number of concerns have been raised about the estrogen-like effects of natural isoflavones (i.e., the possible promotion of estrogen-sensitive cancers) [542–544]. However, a recent nested case-control study and meta-analysis of numerous epidemiological studies show an inverse correlation between GEN intake and breast cancer risk and a number of other clinical studies support the breast and uterine safety of purified naturally derived GEN administered for up to 3 years [545].…”