Hygrolidin is a macrocyclic lactone originally isolated from S. hygroscopicus. It inhibits proliferation of a variety of cancer cell lines, including DLD-1 colon cancer, LNCaP prostate cancer, and K562 leukemia cells (IC50s = 2.9, 5.2, and 33 ng/ml, respectively). Hygrolidin induces the expression and levels of p21 in DLD-1 cells, but not WI-38 fibroblasts, and leads to cell accumulation in the G1 and S phases without inducing apoptosis. It has antiparasitic activity against T. cruzi, L. donovani, and T. b. brucei but also induces cytotoxicity in HepG2 cells (IC50s = 1.1, 72.5, 77, and 24.5 nM, respectively).
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 tumour cells, and inhibits the growth of solid tumour-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.
