Interaction Between Near-Infrared Radiation and Temozolomide in a Glioblastoma Multiform Cell Line: A Treatment Strategy?

Cell Mol Neurobiol. 2021 Jan;41(1):91-104. doi: 10.1007/s10571-020-00835-0. Epub 2020 Mar 31.

Abstract

Photodynamic therapy (PDT) is a potential therapeutic modality against cancer, resulting from the interaction of a photosensitizer (PS) and radiation that generates damage to tumor cells. The use of near-infrared radiation (IR-A) is relevant because presents recognized biological effects, such as antioxidant, neuroprotective and antitumor effects. Glioblastoma is the most aggressive central nervous system (CNS) neoplasm with high proliferation and tissue invasion capacity and is resistant to radio and chemotherapy. Here, we evaluated in vitro the possible interaction of temozolomide (TMZ) with IR-A in a glioblastoma cell line (C6) and in a human keratinocyte cell line (HaCat) how non-tumor cell model, in an attempt to search for a new treatment strategy. The effects of TMZ, IR-A and the interaction between TMZ and IR-A was evaluated by viability exclusion with trypan blue. To perform the interaction experiments, we have chosen 10 μM TMZ and 4.5 J/cm2 of IR-A. From this, we evaluated cytotoxicity, cell proliferation, intracellular reactive oxygen species levels (ROS), as well as the process of cell migration and the P-gp and MRP-1 activity. Cell death mainly due to apoptosis, followed by necrosis, decreased cell proliferation, increased ROS levels, decreased cell migration and decreased P-gp and MRP1 activity were observed only when there was interaction between TMZ and IR-A in the C6 cell line. The interaction between TMZ and IR-A was not able to affect cell proliferation in the HaCat non-tumor cell line. Our results suggest that this interaction could be a promising approach and that in the future may serve as an antitumor strategy for PDT application.

Keywords: Athermic infrared radiation; Glioma; Light-emitting diode; Multidrug resistance phenotype; Photodynamic therapy.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Fluorescence
  • Glioblastoma / therapy*
  • HaCaT Cells
  • Humans
  • Infrared Rays / therapeutic use*
  • Mitotic Index
  • Multidrug Resistance-Associated Proteins / metabolism
  • Necrosis
  • Rats
  • Reactive Oxygen Species / metabolism
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Multidrug Resistance-Associated Proteins
  • Reactive Oxygen Species
  • multidrug resistance-associated protein 1
  • Temozolomide