Thymidine decreases the DNA damage and apoptosis caused by tumor-treating fields in cancer cell lines

Genes Genomics. 2021 Sep;43(9):995-1001. doi: 10.1007/s13258-021-01105-z. Epub 2021 May 5.

Abstract

Background: Tumor-treating fields (TTFields) is an emerging non-invasive cancer-treatment modality using alternating electric fields with low intensities and an intermediate range of frequency. TTFields affects an extensive range of charged and polarizable cellular factors known to be involved in cell division. However, it causes side-effects, such as DNA damage and apoptosis, in healthy cells.

Objective: To investigate whether thymidine can have an effect on the DNA damage and apoptosis, we arrested the cell cycle of human glioblastoma cells (U373) at G1/S phase by using thymidine and then exposed these cells to TTFields.

Methods: Cancer cell lines and normal cell (HaCaT) were arrested by thymidine double block method. Cells were seeded into the gap of between the insulated wires. The exposed in alternative electric fields at 120 kHz, 1.2 V/cm. They were counted the cell numbers and analyzed for cancer malignant such as colony formation, Annexin V/PI staining, γH2AX and RT-PCR.

Results: The colony-forming ability and DNA damage of the control cells without thymidine treatment were significantly decreased, and the expression levels of BRCA1, PCNA, CDC25C, and MAD2 were distinctly increased. Interestingly, however, cells treated with thymidine did not change the colony formation, apoptosis, DNA damage, or gene expression pattern.

Conclusions: These results demonstrated that thymidine can inhibit the TTFields-caused DNA damage and apoptosis, suggesting that combining TTFields and conventional treatments, such as chemotherapy, may enhance prognosis and decrease side effects compared with those of TTFields or conventional treatments alone.

Keywords: Cell division; DNA damage; Thymidine; Tumor‐treating fields; cancer cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Apoptosis / radiation effects
  • BRCA1 Protein / genetics
  • Cell Line, Tumor
  • DNA Damage / genetics*
  • DNA Damage / radiation effects
  • Electromagnetic Fields / adverse effects
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Mad2 Proteins / genetics
  • Magnetic Field Therapy*
  • Proliferating Cell Nuclear Antigen / genetics
  • Thymidine / pharmacology
  • cdc25 Phosphatases / genetics

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • MAD2L1 protein, human
  • Mad2 Proteins
  • PCNA protein, human
  • Proliferating Cell Nuclear Antigen
  • CDC25C protein, human
  • cdc25 Phosphatases
  • Thymidine