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

Area of Science:

• Oncology
• Molecular Biology
• Endocrinology

Background:

• Advanced prostate cancer often develops resistance to antiandrogen therapy.
• This resistance is associated with an aggressive neuroendocrine phenotype.
• Antiandrogens can stimulate peroxisome proliferator-activated receptor gamma (PPARG) signaling, promoting cancer progression.

Purpose of the Study:

• To investigate the adjuvant effects of molecular iodine (I₂) combined with androgen deprivation in prostate cancer.
• To elucidate the role of PPARG in the observed effects of I₂ and androgen deprivation.

Main Methods:

• Utilized androgen-dependent and -independent prostate cancer cell lines.
• Employed TRAMP mice (transgenic adenocarcinoma of the mouse prostate) as an in vivo model.
• Simulated androgen deprivation using bicalutamide, enzalutamide, and charcoal-stripped fetal bovine serum, with and without I₂ treatment.

Main Results:

• I₂ induced cytotoxicity and, in surviving cells, stimulated neurite-like projections, altered lipid content, and reduced invasiveness.
• Combined androgen deprivation and I₂ treatment amplified these effects.
• The PPARG antagonist GW9662 did not block the effects of I₂, indicating a PPARG-independent mechanism.
• In vivo, I₂ increased prostatic desmoplasia in sham mice but did not alter castration-induced effects in TRAMP mice.

Conclusions:

• Molecular iodine (I₂) demonstrates both anti-cancer (cytotoxic, anti-invasive) and pro-cancer (neurite outgrowth, lipid accumulation, desmoplasia) effects.
• These dual actions occur through a mechanism that is independent of PPARG signaling.
• I₂ presents a complex profile warranting further investigation in prostate cancer treatment strategies.