A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells.

Abstract

In this study, screening by LC-MS and cytotoxicity-guided isolation led to the identification of ulleungamide C (1), a previously unknown pipecolic acid-rich branched cyclic depsipeptide, from a soil actinobacterium Streptomyces sp. KCB13F003. The structure of 1 was determined by interpretation of spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments. Antiproliferative assays using mammalian cancerous cells revealed that 1 inhibits the proliferation of HL-60 human promyelocytic leukemia cells. Cell cycle analysis showed an increased accumulation of cells in the G0/G1 phase after treatment with 1. Results of immunoblotting assays revealed that 1 reduced the expression levels of cyclin-dependent kinase 4 (CDK4), CDK6, retinoblastoma protein (Rb), and phosphorylated Rb, whereas it induced cyclin-dependent kinase inhibitor 1B (p27/Kip1) expression.

• Authors: Sangkeun Son, Mina Jang, Byeongsan Lee, Jun-Pil Jang, Young-Soo Hong, Bo Yeon Kim, Sung-Kyun Ko, Jae-Hyuk Jang, Jong Seog Ahn
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 74 Issue 3 Pg. 181-189 (03 2021) ISSN: 1881-1469 [Electronic] England
• PMID: 33208876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Depsipeptides
• Pipecolic Acids
• pipecolic acid

Topics

• Cell Proliferation (drug effects)
• Chromatography, Liquid
• Depsipeptides (chemistry, isolation & purification, pharmacology)
• G1 Phase Cell Cycle Checkpoints (drug effects)
• HL-60 Cells
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, pathology)
• Mass Spectrometry
• Pipecolic Acids (chemistry)
• Resting Phase, Cell Cycle (drug effects)
• Streptomyces (metabolism)