Bevacizumab is superior to Temozolomide in causing mitochondrial dysfunction in human brain tumors

Abstract

Objective: Current chemotherapy treatments available for treating high-grade brain tumors, Temozolomide (TMZ) or Bevacizumab (BEV), not only have specific anti-tumor mechanisms, but also have an effect on mitochondria. However, effects of both drugs on mitochondria isolated from human brain tumors have not been thoroughly investigated. This study determined the direct effects of TMZ and BEV as well as the neurotoxic condition (calcium overload), on the function of mitochondria and compared these effects on mitochondria isolated from low- and high-grade human brain tumors.Methods: Mitochondria were isolated from either low- or high-grade human primary brain tumors. Calcium overload conditions (100 or 200 μM), TMZ (300 μM), and BEV (2 mg/mL) were applied to isolated mitochondria from low- and high-grade brain tumors. Following the treatment, mitochondrial function, including reactive oxygen species production, membrane potential changes, and swelling, were determined. The mitochondrial morphology was also examined.Results: In calcium overload conditions, mitochondrial dysfunction was only found to have occurred in low-grade tumors. In TMZ and BEV treatment, BEV, rather than TMZ, caused greater membrane depolarization and mitochondrial swelling in both grades of brain tumors.Conclusions: TMZ and BEV can directly cause the dysfunction of mitochondria isolated from human brain tumors. However, BEV has a greater ability to disturb mitochondrial function in mitochondria isolated from human brain tumors than either TMZ or calcium overload conditions.