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 IC ₅₀ values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G ₀/G ₁ phase 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.

Graphical abstract

Streptodepsipeptides P11A and P11B were isolated and identified from marine Streptomyces sp. P11-23B and showed significantly antiproliferative activity against glioma cells. Targeting multiple glioma metabolic regulators might be one of the anti-glioma mechanisms of this type of streptodepsipeptides.

Highlights

• •

  Streptodepsipeptides P11A and P11B were isolated from Streptomyces sp.

• •

  Streptodepsipeptides remarkably inhibited proliferation of glioma cells.

• •

  Streptodepsipeptide P11A blocked glioma cell cycle at G ₀/G ₁ phase.

• •

  Streptodepsipeptide P11A downregulated expression of glioma metabolic enzymes.