Acyldepsipeptides inhibit the growth of renal cancer cells through G1 phase cell cycle arrest |
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Authors: | Shan Xu Peng Guo Yang Gao Qi Shi Dalin He Yang Gao Hailong Zhang |
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Affiliation: | 1. Department of Urology, The First Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China;2. Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, Shaanxi, China;3. School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, China |
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Abstract: | 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. |
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Keywords: | Acyldepsipeptide Renal cell carcinoma Cell cycle Antitumor Cyclin D1 |
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