gms | German Medical Science

Objective: Previous investigations revealed that the dipeptide carnosine inhibits the growth of cells derived from malignant glioma. Since it was suggested that carnosine protects non-tumor cells from oxidative stress and alkylating agents, we wondered how tumor cells would respond the treatment with methylglyoxal in combination with carnosine.

Methods: Cells from four different glioblastoma cell lines (T98G, 1321N1, U87 and LN405) were cultivated at different concentrations of carnosine (0, 10, 25 and 50 mM) and methylglyoxal (0, 0.16 and 0.32 mM). After 72 hours, cell-based assays were employed to measure ATP-production and cell membrane integrity as an indicator of necrosis.

Results: Although one line (LN405) did not significantly respond to methylglyoxal if not combined with carnosine and one line (1321N1) did not significantly respond to carnosine if not combined with methylglyoxal, carnosine and methylglyoxal given alone already reduced production of ATP in the other lines. This effect was Although one line (LN405) did not significantly respond to methylglyoxal if it was not combined with carnosine and one line (1321N1) did not significantly respond to carnosine if it was not combined with methylglyoxal, carnosine and methylglyoxal given alone could reduce the production of ATP in the other lines. This effect was observed at different concentrations depending on the line investigated. Most importantly, we observed a very strong synergistic effect between carnosine and methylglyoxal in all cell lines. At the highest concentrations employed (50 mM carnosine and 0.32 mM methylglyoxal), ATP concentration was reduced to 17.48 ± 1.89% (LN405) to 0.52 ± 0.79% (U87) to 8.56 ± 1.06% (1321N1) and to 2.03 ± 0.11% (T98G). A weak indication of necrosis was observed in some cases at the highest concentrations employed, but necrosis was not a prerequisite for the reduced production of ATP.

Conclusions: Carnosine was previously shown to inhibit the growth of cells derived from malignant gliomas as well as those from other tumors. However, although carnosine was able to retard tumor growth even in an animal model, it was not possible to completely abolish tumor growth by carnosine. Therefore, the results obtained in the recent study are highly promising since the very strong synergistic effects observed in combination with methylglyoxal may lead the way to a complete eradication of tumor cells by inhibiting their energy metabolism. Control experiments with isolated rat hepatocytes did not demonstrate a corresponding synergistic reduction of ATP production and therefore, it is possible that the effects observed are specific for tumor cells, at least in the case of glioblastoma.