The effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells lines

Gene. 2019 Nov 15:718:144030. doi: 10.1016/j.gene.2019.144030. Epub 2019 Aug 4.

Abstract

Opioids are widely used in the treatment of cancer related pain. They mainly exert their effects on opioid receptors. The most common opioid in the treatment of pain is morphine. Previous studies show that they may have effects on cancer cell behavior. These may include apoptosis, angiogenesis, invasion, inflammation and immune reactions. Tramadol, also an opioid is widely used in the treatment of cancer pain and is not well studied in cancer behavior. We aimed to investigate the effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells. We used Colo320 (ATCC, CCL-220), Colo741 (ECACC, 93052621) and HCT116 (ATCC, CCL-247) colon cancer cell lines. CD133 was considered colon cancer stem cell marker and used to sort CD133+ and CD133- cells by magnetic cell sorting. MTT (mitochondria-targeted therapeutics) technique was used to detect tramadol's cytotoxic effect on cells in the study groups. Cells were treated with 1 mg/kg, 1.5 mg/kg and 2 mg/kg tramadol for 24 h at 37 °C and 5% CO2.Caspase-3, Ki-67, Bcl-2 and VGEF distributions were performed using indirect immunoperoxidase staining for immunohistochemical analysis. The study showed that tramadol has triggering effect on apoptosis in Colo320 colon cancer stem cells.

Keywords: Cell culture; Colon cancer; Opioids; Tramadol.

MeSH terms

  • Apoptosis / drug effects*
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / metabolism
  • Colonic Neoplasms* / pathology
  • Cytotoxins / pharmacology*
  • HCT116 Cells
  • Humans
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Tramadol / pharmacology*

Substances

  • Cytotoxins
  • Tramadol