Hygrolidin is a 16-membered macrocyclic lactone closely related to the bafilomycins, active against Valsa ceratosperma, the pathogen of apple canker disease. Hygrolidin is active against SV40 tumor cells, and inhibits the growth of solid tumor-derived cell lines such as DLD-1 human colon cancer cells with increased cells in G1 and S phases. Hygrolidin decreases cyclin-dependent kinase (cdk) 4, cyclin D and cyclin B, and increases cyclin E and p21 levels. Hygrolidin-induced p21 inhibits cyclin A-cdk2 complex more strongly than cyclin E-cdk2 complex. It also increases p21 mRNA in DLD-1 cells, but not in normal fibroblasts.