A preliminary study on the impact of nutrient stress induction on drug cytotoxicity in glioblastoma cells and fibroblasts

Abstract

Abstract Background Nutrient stress (NS), one of the hallmarks of the tumour microenvironment, can render cancer cells tolerant to cytotoxicity. Fibroblasts, on the other hand, have cancer cell-like traits, such as plasticity and resiliency. Hence, this study aimed to evaluate the cytotoxicity of the drug on reseeded human U87 glioblastoma (GBM) cells as well as on mouse L929 fibroblasts in the form of monolayer and colonies that grew after NS induction. Results No treatment for 48 h showed a statistically significant difference in U87 cell viability when compared to the 50% hypothetical value. However, temozolomide (TMZ) (151.0 µg/ml) and azithromycin (AZI) (92.0 µg/ml) significantly diminished the number of U87 cell colonies compared to the untreated control, and AZI also outperformed doxycycline (DOXY) (147.0 µg/ml). L929 fibroblasts survived NS, but the cytotoxicity of AZI, DOXY, and AZI + DOXY (92.0 + 147.0 µg/ml) substantially increased than in L929 fibroblasts without NS induction. Conclusions The present findings suggest that NS does not inevitably contribute to cytotoxic drug tolerance in GBM cells. In addition, although fibroblasts can withstand NS, they can also become susceptible to cytotoxic drug-induced death; nevertheless, the type of drug may play a role. Graphical Abstract

Keywords

• Nutrient stress
• Drug cytotoxicity
• Human glioblastoma cells
• Fibroblasts
• Azithromycin
• Doxycycline