Normalizing effect of plant-originated glycoprotein (116 kDa) on G0/G1 arrest in cadmium chloride-induced primary cultured mouse myelocytes.

Cadmium chloride is a well-known carcinogenic and immunotoxic metal chemical, which is commonly found in cigarette smoke and industrial effluent and which is able to cause cell cycle arrest in various cell lines. This study demonstrated that glycoprotein (116 kDa) isolated from Ulmus Davidiana Nakai (UDN) is able to normalize cell cycle arrest caused by cadmium chloride (10 μM, for indicated treatment time in the each experiment) in primary cultured mouse myelocytes. To assess cell cycle arrest, the parameters that are related to the cell cycle evaluated included cytotoxicity, production of intracellular reactive oxygen species (ROS), intracellular Ca(2+) mobilization, the activities of cell cycle-related proteins (p53, p21, and p27), and cyclin D1/cell cyclin-dependent kinase 4 (CDK4) using immunoblot analysis and fluorescence-activated cell sorter analysis. The results in this study showed that UDN glycoprotein (50 μg/ml) inhibits the cytotoxicity, production of intracellular reactive oxygen species (ROS), and intracellular Ca(2+) mobilization brought about by cadmium chloride. With regard to cell cycle-related proteins, UDN glycoprotein (50 μg/ml) significantly suppressed the expression of p53, p21, and p27, whereas it enhanced activity of cyclin D1/CDK4. Taken together, these findings suggest that UDN glycoprotein (50 μg/ml) significantly normalizes arrest of G(0)/G(1) in the cell cycle. Thus, UDN glycoprotein appears to be one compound derived from natural products that is able normalize the calcium chloride-mediated arrest of cell cycle (G(0)/G(1)) in immune cells.