Prostate cancer is a multifocal disease, with varying sensitivity to hormone therapy or androgen deprivation therapy. It is initially responsive to therapies that inhibit androgen receptor (AR) signaling, but the disease eventually advances to an androgen-independent state. Investigators have demonstrated that androgen withdrawal can be a classical stimulator of neuroendocrine (NE) cell differentiation within a certain population of prostate cells. Studies have shown that NE cells increase in population in hormone refractory prostate cancer. In this study, we examined the androgen-responsive human prostate cancer cell line LNCaP. Immunohistochemical profiles of LNCaP cells under conditions that mimic therapeutic androgen ablation versus prostate cancer cells grown in the presence of exogenous androgens established the baseline response. Dibenzoylmethane (DBM) a minor constituent of licorice and known growth inhibitory agent of prostate cancer cells in vitro, was used to induce the NE cell phenotype in LNCaP cells. Preliminary flow cytometric data suggests that LNCaP cells acquire NE characteristics in response to treatment with DBM. Although the molecular mechanisms by which DBM affects the intracellular signaling cascade in prostate cancer are not fully understood, DBM may be seen as both a neuroendocrine receptor modulator and AR modulator with potential therapeutic option for advanced prostate cancer.
