JABOTICABA PEEL EXTRACT (MYRCIARIA JABOTICABA) ENHANCES THE EFFECTS OF ANTIANDROGENIC THERAPY ON THE MIGRATION OF PC-3 PROSTATE CANCER CELLS

Castration-resistant prostate cancer (CRPC) is an aggressive form of the disease that lacks effective treatment, leading to progression, metastasis, and ultimately becoming lethal. The standard protocol for treating this stage of the disease is the androgen deprivation therapy (ADT) using second generation antiandrogenic agents, such as enzalutamide. However, the search for adjuvant therapies able to delay CRPC development without causing significant side effects is an urgent need due to the invariable occurrence of tumor relapse. Previous studies have demonstrated the antioxidant, anti-inflammatory, and anti-obesogenic effects of jaboticaba peel extract (Myrciaria jaboticaba) (JPE), as well as its chemopreventive potential in the development of proliferative lesions in the age-associated prostate microenvironment. Therefore, our study aimed to evaluate the effect of JPE combined with ADT on the viability and migratory capacity of PC-3 CRPC cell line. For this purpose, cell viability was investigated using MTT and Trypan Blue assays. Migratory capacity was assessed through the wound- healing assay using biologically effective doses preselected from the viability assays. Results showed that PC-3 cell viability was affected in a time and dose-dependent manner by JPE treatment, regardless of enzalutamide co-treatment. PC-3 cell viability was significantly inhibited with the highest doses of JPE tested (125, 250, and 500 µg/mL) even following a 24 hour interval. The maximum effect of JPE on viability was observed after 72 hours. Although enzalutamide had a significant effect on cell viability, especially upon prolonged exposure, it did not prevent PC-3 cell migration. Remarkably, though, JPE, both per se or associated with enzalutamide, showed extremely significant inhibition of cell migration even after the shorter exposure interval. Therefore, we conclude that JPE has the potential to delay CRPC progression, overcoming enzalutamide limited effects, especially on tumor cell migratory capacity, thereby making this extract a promising adjuvant agent to improve CRPC treatment.