由聚合物d-乳酸(PDLA)和l-乳酸低聚物形成的立体配合物可能抑制癌细胞的生长并帮助诊断侵袭性癌症——Warburg效应的应用

Joel S Goldberg
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引用次数: 5

摘要

有人提出,聚合物d-乳酸(PDLA)的某些低聚物在体内会与l-乳酸形成立体配合物,导致肿瘤细胞乳酸缺乏。那些利用乳酸转运来维持电中性的癌细胞可能会因为乳酸捕获而停止繁殖或死亡,而那些受益于利用细胞外乳酸的癌细胞可能会受损。细胞内乳酸的捕获与LDH的抑制产生不同的生理反应,因为细胞失去了将丙酮酸转运到另一条途径产生阴离子的选择。与染色或荧光探针结合,PDLA寡聚物可能是诊断组织乳酸和活检标本中可能的细胞分化的一种手段。初步的实验证据证实,高浓度的PDLA具有细胞毒性,l-乳酸与PDLA形成假定的立体复合物。今后的工作应着眼于分离PDLA的生物活性低聚物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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.

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.

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.

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