A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells.
Sangkeun SonMina JangByeongsan LeeJun-Pil JangYoung-Soo HongBo Yeon KimSung-Kyun KoJae-Hyuk JangJong Seog AhnPublished in: The Journal of antibiotics (2020)
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.
Keyphrases
- cell cycle arrest
- cell cycle
- cell death
- induced apoptosis
- pi k akt
- signaling pathway
- cell proliferation
- poor prognosis
- endothelial cells
- electronic health record
- long non coding rna
- binding protein
- molecular docking
- data analysis
- amino acid
- molecular dynamics simulations
- protein kinase
- diabetic rats
- simultaneous determination