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 values ranging from 0.1 μM to 1.4 μM. Streptodepsipeptide P11A was found to block the cell cycle at the G/G 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.

Marine natural products

“…tumour metabolic enzymes, HK2, PFKFB3, PKM2, LLS and FASN were downregulated by 14. 23 A bioassay-guided investigation of a fermentation culture of Pseudonocardia carboxydivorans M-227, which was collected from water at a depth of 3000 m in the Aviles Canyon (Cantabrian Sea, Biscay Bay), yielded two antibiotics, branimycins B 16 and C 17 (ref. 24) that displayed moderate to signicant antibacterial activities against 28 strains (18 Gram-positive; 10 Gram-negative) with MICs ranging from 1 to >160 mg mL À1 .…”

Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

“…Therefore, the effect of TLA on the expression levels of glioma metabolic enzymes, including HK2, PFKFB3, PKM2, and LDH5 in the glycolysis, GLS in the glutaminolysis, and FASN in the lipogenesis, was further investigated. A previous study demonstrated that these metabolic regulators were highly expressed in U87MG and U251 cells [34]. Therefore, the effect of TLA on the expression of these regulators in U87MG and U251 cells was evaluated.…”

Recent Progress of Marine Polypeptides as Anticancer Agents

“…Both P11A and P11B can inhibit the proliferation of several glioma cell lines, with the IC 50 values of 0.1 to 1.4 μM [53]. Streptodepsipeptide P11A induced apoptosis and inhibited the cell cycle at the G0/G1 phase in glioma cells [53]. Further study showed that streptodepsipeptide P11A downregulated the expressions of important tumor metabolic enzymes such as HK2, GLS, PKM2, PFKFB3, and FASN [53].…”

“…P11-23B (CN106167517) [9]. Both P11A and P11B can inhibit the proliferation of several glioma cell lines, with the IC 50 values of 0.1 to 1.4 μM [53]. Streptodepsipeptide P11A induced apoptosis and inhibited the cell cycle at the G0/G1 phase in glioma cells [53].…”

“…Streptodepsipeptide P11A induced apoptosis and inhibited the cell cycle at the G0/G1 phase in glioma cells [53]. Further study showed that streptodepsipeptide P11A downregulated the expressions of important tumor metabolic enzymes such as HK2, GLS, PKM2, PFKFB3, and FASN [53]. Sansalvamide A (US7709443) [10], a cyclic depsipeptide produced by a ma-rine fungus, has potent antitumor activity [54].…”