Anticancer effects of novel NSAIDs derivatives on cultured human glioblastoma cells

Z Naturforsch C J Biosci. 2020 Sep 5;76(7-8):329-335. doi: 10.1515/znc-2020-0093. Print 2021 Jul 27.


Several epidemiologic, clinical and experimental reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) could have a potential as anticancer agents. The aim of this study was the evaluation of cytotoxic potential in human glioblastoma cells of novel synthesized NSAID derivatives, obtained by linking, through a spacer, α-lipoic acid (ALA) to anti-inflammatory drugs, such as naproxen (AL-3, 11 and 17), flurbiprofen (AL-6, 13 and 19) and ibuprofen (AL-9, 15 and 21). The effects on the level of gene expression were also determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. According to our results, NSAID derivatives exhibited concentration dependent cytotoxic effects on U87-MG cell line when compared with the control group. Moreover, treatment of the most active compounds (AL-3, AL-6 and AL-9) caused upregulation of tumor suppressor gene PTEN and downregulation of some oncogenes such as AKT1, RAF1 and EGFR. In conclusion, our results revealed that AL-3, AL-6 and AL-9 could be suitable candidates for further investigation to develop new pharmacological strategies for the prevention of cancer.

Keywords: AKT1; NSAIDs; PTEN; antiproliferative action; glioblastoma.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Dose-Response Relationship, Drug
  • ErbB Receptors / genetics
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Molecular Structure
  • NF-kappa B p50 Subunit / genetics
  • PTEN Phosphohydrolase / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • KRAS protein, human
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • PTEN Phosphohydrolase
  • Proto-Oncogene Proteins p21(ras)