gms | German Medical Science

Objective: Despite ongoing research efforts, glioblastoma (GBM) still has a poor prognosis even under standard therapy, combining temozolomide (Tmz) and irradiation (Rx). Here, we investigated whether the dipeptide carnosine (β-alanine-L-histidine; Car), which reduces growth, migration and metastasis of glioblastoma cells in vitro, affects the response of glioblastoma cells to standard therapy.

Methods: Cells from six GBM cell lines were incubated for 24 hours with Tmz (200 µM) or Car (50 mM), with a combination of both compounds or without compounds for control. Then, cells were irradiated by 8 Gy before they received fresh medium with or without compounds, which was repeated after 3 days. After 7 days, viability of each cell line was determined in sextuplicate by measuring ATP in cell lysates.

Results: Compared to the untreated control group, all cells responded to the presence of Car with a significant (p < 0.0005) reduction of viability between 32.0±3.8% and 60.8±4.1%, whereas Tmz was not effective in 2 cell lines (G55T2 and T98G) and effective in the 4 others (LN405, U87, U373, LN229; 69.3±4.5% to 39.0±2.1% viability; all p < 0.0005). In all cases, a combination of Car with Tmz was more effective than treatment with Car or Tmz alone (all p < 0.0005) including the Tmz non-responding cells (G55T2: Car: 57.6±3.5% and Car+Tmz 22.4±1.0%; T98G: Car: 49.3±2.8% and Car+Tmz: 33.2±2.8%). In all cells, radiation alone reduced viability between 55.6±2.8% and 90.1±4.3% (p < 0.05) and an additive effect of Tmz on radiation was observed also in the Tmz non-responding cells (G55T2: Rx: 81.4±1.6% and Rx+Tmz: 57.6±3.7%; T98G: Rx: 56.0±2.5% and Rx+Tmz: 47.4±4.0%; both p < 0.005). Irradiation of Car treated cells always resulted in a further decrease of viability (13.8±0.8% to 41.0±2.9%; p < 0.05) and a maximum reduction of viability between 8.5±0.5% and 20.1±1.3% was achieved when cells were exposed to both compounds under irradiation.

Conclusion: In all GBM cell lines a resistance to carnosine treatment has not been observed. Furthermore, the dipeptide does not protect cells from the toxic effects of irradiation or Tmz treatment. Combined with standard therapy (Rx + Tmz) carnosine enhanced the effectivity of this treatment in the cell culture model employed by a factor of 1.7±0.27. Therefore, carnosine may be considered as an adjuvant to standard therapy.