Phenolic zingerone nanoparticles impede cell cycle progression to compete against human urothelial carcinoma.

Civilization diseases including cancer are caused by more than 80 % of worldwide lethal. Phytochemicals-based methodologies for cancer chemoprevention, adjuvant chemotherapy, and anti-carcinogenic progression have caught the attention of modern medicines and become one of the explicit trends for cancer prevention and therapeutic strategies. In this study, we fabricated the phytochemical-derived zingerone nanoparticles (NPs) and examined their effects on anti-tumorigenicity and the related signaling mechanisms in two human urothelial carcinoma (UC) BFTC905 and BFTC909 cell lines. Our results demonstrated that zingerone NPs significantly elicited cytotoxicity and inhibited in vitro tumorigenesis in these human UC cells. Moreover, zingerone NPs impeded cell cycle progression and induced cell apoptosis in a dose-dependent manner. TUNNEL assay further supported that zingerone NPs markedly triggered cell apoptosis. Molecular mechanisms analysis further demonstrated that zingerone NPs dramatically interfered with CDKs and Cyclins involved in cell cycle progression including inhibition of CDK6, CDK4 and Cyclin D1, CDK2 and Cyclin A2, and CDK1 and Cyclin B1, in the G1, S, and G2/M phases respectively. Interestingly, TCGA database analysis also indicated that upregulation of cell cycle transition factors such as CDK4 and Cyclin D1 in the G1 phase, CDK2 and Cyclin A2 in the S phase, and CDK1 and Cyclin B1 in the G2/M phase are highly correlated with advanced stages in bladder carcinoma patients. Altogether, our findings suggest that phytochemical-derived zingerone NPs can be a potent adjuvant agent to provide beneficial chemopreventive and anti-tumorigenesis strategies for human urothelial carcinoma.