Jaboticaba peel extract attenuates mesenchymal behavior and vasculogenic mimicry in castration-resistant prostate cancer cells under enzalutamide treatment.

Jaboticaba (Plinia cauliflora) is a Brazilian fruit rich in bioactive substances that are concentrated in the fruit peel. Accordingly, jaboticaba peel extract (JPE) has emerged as a potential adjuvant therapy against prostatic lesions due to its antioxidant and chemopreventive properties verified in the prostatic microenvironment associated with senescence and hormone-dependent prostate cancer (PCa). At the same time, it is known that disease progression involves mechanisms of tumor neovascularization, such as vasculogenic mimicry (VM), which is frequently associated with therapeutic resistance. Therefore, this study aimed to expand previous investigations into the context of castration-resistant prostate cancer (CRPC) by evaluating the modulation of cellular plasticity mechanisms, such as VM and epithelial-mesenchymal transition (EMT), in response to treatment with JPE, either alone or in combination with androgen ablation induced by enzalutamide. Results indicated that the CRPC cell line PC-3 exhibits greater resistance to both therapies when compared with the androgen-dependent LNCaP cell line. Despite this, JPE demonstrated the ability to inhibit the invasion and migration of PC-3 cells, in addition to negatively modulating the acquisition of mesenchymal traits and the formation of VM by these cells upon exposure to enzalutamide. Thus, our in vitro findings demonstrate that although its antitumor actions are more pronounced under hormonal dependence conditions, JPE also has potential as an adjuvant therapy in the treatment of CRPC, particularly by impairing tumor cell mesenchymal behaviors, such as increased migratory capacity and the formation of vascular channels through VM.