Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G)

Biomed Pharmacother. 2017 Aug;92:254-264. doi: 10.1016/j.biopha.2017.05.050. Epub 2017 May 24.

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain cancer that causes high mortality in humans. It responds poorly to the most common cancer treatments, such as surgery, chemo- and radiation therapy. Temozolomide (TMZ) is an alkylating agent that has been widely used to treat GBM; resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. In this study, we evaluated the potential synergistic effect of 100μM TMZ and EMF (100Hz, 100G) on two human glioma cells line, i.e., U87 and T98G above single treatments, TMZ or EMF. Co-treatment synergistically enhanced apoptosis in U87 and T98G cells, by increasing the expression of P53, Bax, and Caspase-3 and decreasing that of Bcl-2 and Cyclin-D1. We also observed an increase in reactive oxygen species (ROS) production and the overexpression of the heme oxygenase-1 (HO-1) gene in comparison to controls. In conclusion, since EMF enhanced the apoptotic effect of TMZ, possibly through a redox regulation mechanism, the TMZ/EMF combination may be effective for glioma cancer treating. Further studies are needed to reveal the action mechanism of this possible novel therapeutic approach.

Keywords: Apoptosis; Extremely low frequency-electromagnetic field (ELF-EMF); Glioblastoma multiforme (GBM); Human glioblastoma cells (U87 and T98G); Necrosis; Temozolomide (TMZ).

MeSH terms

  • Antineoplastic Agents, Alkylating / toxicity*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cytotoxins / toxicity*
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / toxicity
  • Electromagnetic Fields / adverse effects*
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Magnetic Field Therapy / methods
  • Temozolomide

Substances

  • Antineoplastic Agents, Alkylating
  • Cytotoxins
  • Dacarbazine
  • Temozolomide