关键词: Prodigiosin cancer metabolism glucose transporter glycolysis

来  源:   DOI:10.1080/14786419.2024.2367241

Abstract:
In contrast to normal cells, cancer cells predominantly utilise glycolysis for ATP generation under aerobic conditions, facilitating proliferation and metastasis. Targeting glycolysis is effective for cancer treatment. Prodigiosin (PDG) is a natural compound with various bioactivities, including anticancer effects. However, the precise action mechanisms and molecular targets of PDG, which has demonstrated efficacy in regulating glucose metabolism in cancer cells, remain elusive. Here, we aimed to investigate the anti-cancer activity of PDG and mechanism in cancer metabolism. PDG regulated cancer metabolism by suppressing intracellular ATP production rate and levels. It inhibited glycolysis and mitochondrial oxidative phosphorylation, impeding ATP production dependent on both glycolysis and mitochondrial respiration. Moreover, it inhibited cellular glucose uptake by directly interacting with glucose transporter 1 without affecting its mRNA or protein levels in HCT116 cells. We provide insights into the anti-cancer effects of PDG mediated via cancer metabolism regulation, suggesting its therapeutic potential for cancer.
摘要:
与正常细胞相反,癌细胞主要利用糖酵解在有氧条件下产生ATP,促进增殖和转移。靶向糖酵解对于癌症治疗是有效的。Prodigiosin(PDG)是一种具有多种生物活性的天然化合物,包括抗癌作用。然而,PDG的精确作用机制和分子靶标,已经证明了在调节癌细胞葡萄糖代谢方面的功效,仍然难以捉摸。这里,我们旨在研究PDG的抗癌活性和在癌症代谢中的作用机制。PDG通过抑制细胞内ATP产生速率和水平来调节癌症代谢。它抑制糖酵解和线粒体氧化磷酸化,阻碍ATP的产生依赖于糖酵解和线粒体呼吸。此外,它通过直接与葡萄糖转运蛋白1相互作用而抑制细胞葡萄糖摄取,而不影响其在HCT116细胞中的mRNA或蛋白质水平。我们提供了通过癌症代谢调节介导的PDG的抗癌作用的见解,表明它对癌症的治疗潜力。
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