Acyldepsipeptides inhibit the growth of renal cancer cells through G1 phase cell cycle arrest.
Acyldepsipeptides are a group of potent antibiotics discovered in the secondary metabolites of Streptomyces species. However, besides the function of antibiotics, no other activities have been reported about these important compounds so far. In the course of searching the natural products as chemotherapeutic agents for renal cell carcinoma, we found that ADEP1, a major metabolic component of Streptomyces hawaiiensis NRRL 15010, could effectively inhibit the growth of 786-O, 769-P, and ACHN renal carcinoma cells in MTT assay. Flow cytometric analysis demonstrated that ADEP1 could block the cell cycle arrested at G1 phase. Moreover, it was found that ADEP1 down-regulated the expressions of cyclin D1, CDK4 and PCNA and inhibited activity of MAPK-ERK pathway by detection of decreased expression of phosphorylated ERK1/2 and c-Fos in 786-O and 769-P cells by Western blotting. To our knowledge, this is the first report concerning to the antitumor activities of acyldepsipeptides. Based on these results, ADEP1 may become a promising lead compound to be developed a novel chemotherapeutic agent for treatment of renal carcinoma.
Department of Urology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Shan
S
Xu
Peng
P
Guo
Yang
Y
Gao
Qi
Q
Shi
Dalin
D
He
Yang
Y
Gao
Hailong
H
Zhang
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell; D019938:Cyclin D1 / Q000096:biosynthesis; D047630:Depsipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D016193:G1 Phase / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use
C584118:ADEP1 compound; C584119:ADEP2 compound; D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D010456:Peptides, Cyclic; D019938:Cyclin D1
Acyldepsipeptide; Antitumor; Cell cycle; Cyclin D1; Renal cell carcinoma