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.
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Acknowledgements
We thank Harumi Aono, Kai Yamamoto, Dr. Junnosuke Otaka, and Dr. Yushi Futamura in RIKEN Center for Sustainable Research Science for preliminary bioactivity tests. We also thank Dr. Shunji Takahashi in RIKEN for his helpful discussion about the ulleungamide family. This work was supported by the KRIBB Research Initiative Program and the R&D Convergence Program (CAP-16-03-KRIBB) of the National Research Council of Science and Technology (NST) funded by the Ministry of Science ICT (MIST) of the Republic of Korea. We thank the KBSI, Ochang, Korea, for providing the NMR and HRESIMS data.
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Son, S., Jang, M., Lee, B. et al. A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells. J Antibiot 74, 181–189 (2021). https://doi.org/10.1038/s41429-020-00385-z
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DOI: https://doi.org/10.1038/s41429-020-00385-z
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