title: Destruxin E, a cyclodepsipeptide antibiotic, reduces cyclin D1 levels and inhibits anchorage-independent growth of v-Ki-ras-expressed pMAM-ras-REF cells.
abstract: Destruxin E (DE), a cyclodepsipeptide isolated from fermentation broths of Metarhizium sp. MA324, inhibited the growth of v-Ki-ras-expressed pMAM-ras-REF (rasREF) cells in the suspension (anchorage-independent) culture (a) more strongly than that in the substratum-attached (anchorage-dependent) culture (b) or that of v-Ki-ras-unexpressed pMAM-ras-REF (REF) cells in the substratum-attached culture (c); the IC(50) values of DE were 0.07 microM (a), 0.4 microM (b), and 1.2 microM (c). DE arrested G1 phase cell cycle progression of rasREF cells in the substratum-attached culture (b). In rasREF cells treated with DE for 72 h in suspension culture (a), the levels of cyclin D1, cyclin A, p27(Kip1), and hyperphosphorylated Rb were decreased, but the levels of cdk4, cdk6, cdk2, p16(INK4a), and p21(Cip1) were not affected. Among these effects, the decrease in cyclin D1 was prominent. DE decreased the level of cyclin D1 in rasREF cells in the suspension culture (a) at 0.1 microM and in the substratum-attached culture (b) at 1 microM, while the level of cyclin D1 in REF cells in the substratum-attached culture (c) was not decreased at 1 microM. The extent of growth inhibition correlated with the decrease in cyclin D1. The level of cyclin D1 mRNA of rasREF cells in the suspension culture (a) was also decreased by DE. DE decreased cyclin D1 mRNA, resulting in inhibition of anchorage-independent growth of rasREF cells.
authors.affiliation: Showa Pharmaceutical University, 3-3165 Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Souichi
authors.initials: S
authors.lastname: Ikeno
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hosokawa
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
authors.forename: Makoto
authors.initials: M
authors.lastname: Hori
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tsuchiya
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005656:Fungal Proteins / Q000494:pharmacology*; D016193:G1 Phase; D011905:Genes, ras; D006131:Growth Inhibitors / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D005656:Fungal Proteins; D006131:Growth Inhibitors; D019938:Cyclin D1; D018631:ras Proteins; C040425:destruxin E