Nanosized Ginger‐Derived Phenolic Zingerone Obstructs Cell Cycle G2/M Progression and Initiates Apoptosis in Human Colorectal Cancer

ABSTRACT Colorectal cancer (CRC) has become one of the most arduous challenges in contemporary cancer treatment. In nanomedicine, biomedical methodologies and nanomaterials are combined to develop novel and effective treatments for illnesses, infections, and cancer. The characteristics of nanotechnology are promising for addressing the urgent problems of modern cancer therapeutics, such as tumor recurrence, multidrug resistance, and the limited accessibility of drugs to tumor tissue. Plant‐derived natural chemicals, termed phytochemicals, have bioactive characteristics, including anticarcinogenesis, promoted cell apoptosis, antioxidation, antiproliferation, and anti‐inflammatory effects. Zingerone is a phenolic compound; it is one of the nonvolatile pungent constituents of ginger and has various pharmacological activities. Here, we fabricated phytochemical‐derived zingerone nanoparticles (NPs) and explored their anti‐cell viability and anti‐tumorigenicity effects on human CRC LoVo and HCT116 cell lines. Moreover, zingerone NPs significantly inhibited cell viability and in vitro tumorigenicity. Next, flow cytometry analysis revealed that zingerone NPs markedly suppressed cell cycle progression in the G2/M phase compared to the G1/S phase and significantly promoted cell apoptosis in a dose‐dependent manner in these CRC cell lines. Western blot analysis also suggested that zingerone NPs mediate cell apoptosis by upregulating caspase 3/PARP signaling. Additionally, zingerone NPs significantly restricted CDC25C‐mediated CDK1/Cyclin B1 signaling activation in the G2/M phase and Cyclin D/CDK2/Cyclin A signaling downregulation in the G1/S phase. Zingerone NP‐mediated p21 upregulation also decreased CDK activity and interfered with cell cycle progression. Indeed, TCGA data analysis also suggested that CDC25C and CDK1 upregulation were correlated with advanced tumor stage in colorectal cancer patients. Taken together, these results indicated that zingerone NPs significantly disrupt cell cycle progression and induce apoptosis in human CRC cells. Our findings indicate that phytochemical‐derived zingerone NPs may serve as a potential chemopreventive adjuvant agent and therapeutic strategy for human colorectal cancer.