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Biochem Biophys Res Commun. 2002 Oct 18;298(1):178-83.
Hygrolidin induces p21 expression and abrogates cell cycle progression at G1 and S phases.
Kawada M, Usami I, Ohba S, Someno T, Kim J, Hayakawa Y, Nose K, Ishizuka M.
Institute for Chemotherapy, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka-ken 410-0301, Japan.
Hygrolidin family antibiotics showed selective cytotoxicity against both cyclin E- and cyclin A-overexpressing cells. Among them, hygrolidin was the most potent and inhibited growth of solid tumor-derived cell lines such as DLD-1 human colon cancer cells efficiently more than that of hematopoietic tumor cells and normal fibroblasts. FACS analysis revealed that hygrolidin increased cells in G1 and S phases in DLD-1 cells. While hygrolidin decreased amounts of cyclin-dependent kinase (cdk) 4, cyclin D, and cyclin B, it increased cyclin E and p21 levels. Hygrolidin-induced p21 bound to and inhibit cyclin A-cdk2 complex more strongly than cyclin E-cdk2 complex. Furthermore, hygrolidin was found to increase p21 mRNA in DLD-1 cells, but not in normal fibroblasts. Thus, hygrolidin inhibited tumor cell growth through induction of p21. In respect to p21 induction, inhibition of vacuolar-type (H+)-ATPase by hygrolidin was suggested to be involved.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12379237&dopt=Abstract
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