Solanum lycopersicum and Olea europaea microRNAs as Epithelial-Mesenchymal-Transition regulators in prostate cancer

Prostate cancer (PC) is the second most common malignancy among men worldwide. Treatment options for advanced or aggressive metastatic PC, especially if castration-resistant, often yield suboptimal outcomes and rarely achieve a cure. This underscores the urgent need for improved preventive and therapeutic strategies. In recent years, plant-derived microRNAs (miRs) have emerged as potential epigenetic regulators across kingdoms, influencing processes such as tumor development and progression, thus offering new avenues for cancer prevention. Based on in vitro and in vivo studies a recently developed food supplement based on 98 % heated/spray dried whole tomato (Solanum lycopersicum L.) and 2% olive wastewater (Olea europaea L.) - key nutrients of the Mediterranean diet – appears to offer a translational potential in this context. Here we investigate the antitumor activity of the miRs present in the water-soluble fraction of the supplement (TOFS miRs), on the aggressive prostate cancer cell line PC3. TOFS miRs were extracted, quantified, and analyzed by qRT-PCR, identifying miRNAs from 25 families with known human targets involved in tumorigenesis. To this end multiparametric biochemical and functional assays were performed using PC3 prostate cancer cells to establish whether miRNAs can module cell motility and epithelial-mesenchymal transition. The results indicate that TOFS miRs modulate key cellular processes in PC3 cells, particularly their migratory activity through the regulation of epithelial-mesenchymal transition (EMT)-related genes. This finding further characterizes the nutrient complex of the supplement, which has been shown to modulate experimental prostate carcinogenesis and to provide clinical benefits in benign prostatic hyperplasia in humans.