Renner Christof, Asperger Ansgar, Seyffarth Anne, Meixensberger Jürgen, Gebhardt Rolf, Gaunitz Frank
Klinik und Poliklinik für Neurochirurgie, Medizinische Fakultät der Universität Leipzig, Leipzig, Germany.
Neurol Res. 2010 Feb;32(1):101-5. doi: 10.1179/016164109X12518779082237. Epub 2009 Nov 11.
Recently, it was revealed that carnosine inhibits growth of cells isolated from human malignant glioma. In order to understand how this effect is mediated, experiments were performed that addressed a possible influence of carnosine on energy metabolism.
Cells from the glioma line T98G and primary cultured cells from human malignant glioma were cultivated in the presence of carnosine and inhibitors of cellular energy metabolism. As a specific inhibitor for anaerobic glycolysis, oxamate, and as an inhibitor for mitochondrial oxidative phosphorylation, potassium cyanide, were used, and the influence on ATP production was determined using cell-based assays.
The experiments identified glycolysis as crucial for ATP production in gliomas. In addition, ATP production by mitochondrial activity did not significantly contribute to ATP production and carnosine was identified to be an inhibitor of the vital anaerobic glycolysis.
Carnosine might be considered as a potential drug for the treatment of malignant glioma or other tumors since it inhibits the glycolytic energy metabolism that is crucial for cancer cells and malignant gliomas as shown in the current study. This is especially interesting since the dipeptide is a naturally occurring substance that should be well tolerated.
最近有研究表明,肌肽可抑制从人类恶性胶质瘤中分离出的细胞生长。为了了解这种作用是如何介导的,我们进行了实验,探讨肌肽对能量代谢的可能影响。
在存在肌肽和细胞能量代谢抑制剂的情况下,培养胶质瘤细胞系T98G的细胞以及人类恶性胶质瘤的原代培养细胞。使用草氨酸作为无氧糖酵解的特异性抑制剂,使用氰化钾作为线粒体氧化磷酸化的抑制剂,并通过基于细胞的检测方法确定对ATP产生的影响。
实验确定糖酵解对胶质瘤中的ATP产生至关重要。此外,线粒体活性产生的ATP对ATP产生的贡献不显著,并且肌肽被确定为重要的无氧糖酵解抑制剂。
由于肌肽抑制了糖酵解能量代谢,而糖酵解能量代谢对癌细胞和恶性胶质瘤至关重要,如本研究所示,因此肌肽可被视为治疗恶性胶质瘤或其他肿瘤的潜在药物。这一点尤其有趣,因为这种二肽是一种天然存在的物质,应该具有良好的耐受性。