The Role of Curcumin in Prostate Cancer Cells and Derived Spheroids

SIMPLE SUMMARY: In recent years, considerable efforts have been made to discover new compounds useful for prostate cancer (PC) therapy and related clinical management. Promising advances in this field were reached with nutraceutical compounds. Curcumin represents an attractive therapeutic agent for mCRPC patients. Curcumin treatment displayed a dose-dependent reduction of DU145 and PC-3 PC cell viability similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, by exploring the EGFR-mediated signaling, we observed that the treatment with both chemotherapeutic agents and curcumin reduced EGFR expression levels and ERK activation. Finally, we demonstrated that curcumin reduces the size of DU145 and PC-3 3D cell spheroids and has the potential to induce apoptosis. ABSTRACT: A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially available nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moderate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids.