title: Antiproliferative cyclodepsipeptides from the marine actinomycete Streptomyces sp. P11-23B downregulating the tumor metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis.
abstract: Two cyclodepsipeptides and a known cyclodepsipeptide valinomycin were isolated from a culture of the marine actinomycete Streptomyces sp. P11-23B. Their structures were established based on NMR, HRESIMS, and MS-MS spectroscopic interpretation as well as by chemical degradation. Both streptodepsipeptides P11A and P11B inhibited proliferation of different glioma cell lines, with IC50values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G0/G1phase and induce apoptosis in glioma cells. Further investigation demonstrated that streptodepsipeptide P11A downregulated expression of HK2, PFKFB3, PKM2, GLS, and FASN, important tumor metabolic enzymes. Data from this study suggested that targeting multiple tumor metabolic regulators might be one anti-glioma mechanism of streptodepsipeptide P11A. A possible mechanism for this class of streptodepsipeptides is reported herein.
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Ye
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Komal
authors.initials: K
authors.lastname: Anjum
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Song
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Wang
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Mengxuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China.
authors.forename: Haocai
authors.initials: H
authors.lastname: Huang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: xylian@zju.edu.cn.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Lian
authors.affiliation: Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China. Electronic address: zzhang88@zju.edu.cn.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D039903:Actinobacteria / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D050155:Lipogenesis / Q000187:drug effects; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides
keywords: Antiproliferative agents; Cyclodepsipeptides; Glioma cells; Marine actinomycete; Streptomyces sp.; Tumor metabolic regulators