Introduction: Castration resistant prostate cancer (CRPC) represents a challenge in urologic oncology. Several treatments are available for this tumor, but their efficacy tends to reduce in time. In recent years, several natural compounds have been tested as possible adjuvant treatment in CRPC patients. Among the other curcumin (CU) showed interesting bioactive properties, but low penetration within cells. We hypothesized that the combination with lactoferrin (LF) might exert a synergistic effect on prostatic cancer cells as anti-cancer. Their effects have been evaluated in PC3 and DU145 prostate cancer cells, that are in vitro models of CRPC. Methods: Human CRPC cell lines (DU-145, PC3) were cultured in medium added with or without LF (175 µM) ± CU (2.5 µg/ml and 5 µg/ml). Cell viability was determined using a standard colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) reduction assay. To test ability of cell migration observation at 6 and 24 h after scratch wounds were made. Quantitative Real-time PCR was performed to evaluate gene expression of death receptors (DR) and integrins (a3/ß1). The human annexin V ELISA assay was used for the quantitative detection of annexin V, involved in apoptosis regulation. Results: In PC3 cells, the proliferation rate is reduced by treatments alone or in association, with a significant reduction in presence of CU, both at 2.5 (p=0.007) and 5 ug/ml (p=0.001), in a dose-dependent manner. In DU145 cells, the inhibitory effect of CU is more significant in presence of LF. In PC3 migration, LF significantly weakened invasion capacity with an increase of the cell-free area of 24.9%, 31.8%, and 24% respectively in presence of LF alone, CU2.5+LF and CU5+LF, after 6h, with similar results in DU145 cells. In accord the integrins a3 / ß1, showed a significant reduction in both prostate cell lines, in presence of CU2.5, CU5, and LF175 and their combination (p < 0.005). Moreover, in PC3 and DU145 an upregulation of pro-apoptotic DR4 and DR5 gene expression have been observed. Finally, in both PC3 and DU145 cells line an increased concentration of human annexin V, a marker of apoptosis, have been recorded(p < 0.005). Conclusions: Our results showed that the association of CU and LF might led to beneficial effect on CRPC prostate cancer reducing the proliferative activity of cancerous cells and their ability to migrate and produce metastases. In addition, we can suggest a potential pro-apoptotic effect of CU and LF leading to a potential application as an adjuvant treatment for the treatment of CRPC. SOURCE OF Funding: No source of funding
