Molecular Iodine Induces Anti- and Pro-Neoplastic Effects in Prostate Cancer Models

Advanced prostate cancer frequently develops resistance to antiandrogen therapy and acquires an aggressive neuroendocrine phenotype. Antiandrogens stimulate peroxisome proliferator-activated receptor gamma (PPARG) signaling and cancer progression. Molecular iodine (I2) induces cytotoxic effects in prostate cancer cell lines and antineoplastic effects in neuroblastoma and breast cancer through the indirect activation of PPARG. We investigated the adjuvant effects of I2 and androgen deprivation in prostate cancer, as well as the role of PPARG in these projections. We used androgen-dependent and androgen-independent cell lines and TRAMP mice (transgenic adenocarcinoma of the mouse prostate) as biological models, as well as bicalutamide (Bic), enzalutamide (Enz), and charcoal-stripped fetal bovine serum (CS-FBS) as androgen deprivation models. I2 promoted cytotoxic effects, whereas in surviving cells, it stimulated the outgrowth of neurite-like projections, regulated lipid content, and reduced invasive capacity. Androgen deprivation plus I2 magnified these effects, while GW9662 (PPARG antagonist) did not block them. In vivo, I2 increased the degree of prostatic desmoplasia in the sham mice but did not amplify the stromal response or reduce the epithelial lesion score induced by castration in TRAMP. In conclusion, I2 showed anti-cancer (cytotoxic, anti-invasive) and pro-cancer (pro-neurite, lipid accumulation, desmoplasia) effects through a PPARG-independent mechanism.