Dark-colored maple syrup treatment induces S-phase cell cycle arrest via reduced proliferating cell nuclear antigen expression in colorectal cancer cells

Maple syrup is a natural sweetener that is consumed worldwide. It has been previously reported that dark-colored maple syrup exerts an inhibitory effect on colorectal cancer (CRC) proliferation and invasion. In the present study, the underlying mechanism of CRC cell growth inhibition was examined with dark-colored maple syrup treatment using a shotgun liquid chromatography-tandem mass spectrometry-based global proteomic approach. Applying a semi-quantitative method based on spectral counting, 388 proteins were identified with expression changes of >1.5-fold following dark-colored maple syrup treatment. Gene Ontology analysis revealed that these proteins possessed cell cycle-associated functions. It was also indicated that CRC cells treated with dark-colored maple syrup exhibited decreased proliferating cell nuclear antigen (PCNA) expression and S-phase cell cycle arrest. Dark-colored maple syrup treatment also resulted in altered expression of cell cycle-associated genes, including cyclin-dependent kinase (CDK)4 and CDK6. In conclusion, these data suggested that dark-colored maple syrup induced S-phase cell cycle arrest in CRC cells by reducing the expression of PCNA and regulating cell cycle-associated genes. These findings suggest that dark-colored maple syrup may be a source of compounds for the development of novel drugs for colorectal cancer treatment.