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 synthesized the phytochemical-derived zingerone nanoparticles (NPs). We examined the effects of zingerone NPs-mediated anti-cell growth and the related signaling mechanisms on two human urothelial carcinoma (UC) BFTC905 and BFTC909 cell lines.

Our results demonstrated that zingerone NPs significantly elicited cytotoxicity and effectively inhibited tumorigenesis in vitro 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 also demonstrated that zingerone NPs dramatically interfered with protein regulation in G1, S, and G2/M phases progression including inhibition of CDK6 and Cyclin D1, CDK2 and Cyclin A2, and CDK1 and Cyclin B1, respectively. Simultaneously, zingerone NPs modulated the upregulation of cell cycle inhibitors such as p21, p27, and p53 were also observed.Interestingly, TCGA database analysis also shows that upregulation of cell cycle transition factors such as Cyclin A2 and CDK2 in the S phase, and Cyclin B1 and CDK1 in the G2/M phase are highly correlated with advanced stages in bladder carcinoma patients.

Altogether, these results suggest that phytochemical-derived zingerone NPs may be a potent adjuvant agent, providing a beneficial chemoprevention and anti-tumorigenesis on human bladder carcinoma.