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由聚d-乳酸(PDLA)和l-乳酸的特定低聚物形成的立体复合物可能抑制癌细胞生长并有助于诊断侵袭性癌症——瓦伯格效应的应用。

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.

作者信息

Goldberg Joel S

机构信息

Durham Veterans Affairs Medical Center and Duke University School of Medicine.

出版信息

Perspect Medicin Chem. 2011 Feb 15;5:1-10. doi: 10.4137/PMC.S6229.

Abstract

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA.

摘要

有人提出,聚合物d-乳酸(PDLA)的特定低聚物将在体内与l-乳酸形成立体复合物,导致肿瘤细胞中乳酸缺乏。那些利用乳酸转运来维持电中性的癌细胞可能会因乳酸捕获而停止增殖或死亡,而那些受益于细胞外乳酸利用的癌细胞可能会受到损害。与抑制乳酸脱氢酶(LDH)相比,细胞内乳酸捕获产生的生理状态不同,因为细胞失去了将丙酮酸转运至替代途径以产生阴离子的选择。与染料或荧光探针结合后,PDLA低聚物可能成为诊断活检标本中组织乳酸以及可能的细胞分化的试剂。初步实验证据表明,高浓度的PDLA具有细胞毒性,并且l-乳酸与PDLA形成了假定的立体复合物。未来的工作应致力于分离具有生物活性的PDLA低聚物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd6f/3072648/f791ec970109/pmc-2011-001f1.jpg

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