Curcumin exerts cytotoxicity dependent on reactive oxygen species accumulation in non-small-cell lung cancer cells

Future Oncol. 2019 Apr;15(11):1243-1253. doi: 10.2217/fon-2018-0708. Epub 2019 Mar 7.

Abstract

Aim: Curcumin induces cytotoxic cell death in several human cancer cells. Here, we have investigated the effects of curcumin on non-small-cell lung cancer (NSCLC) with an aim to identify underlying mechanisms of its cytotoxic effect.

Materials & methods: The effects of various concentrations of curcumin on the NSCLC cell lines A549 and SPC-A1 were evaluated by MTT assay, colony-forming assay and flow cytometry. Additionally, protein expression associated with different signaling pathways was assessed using western blotting.

Results: Curcumin exhibited cytotoxicity against NSCLC, evident from the inhibition of cell proliferation, G2/M arrest, DNA damage, endoplasmic reticulum stress and mitochondrial apoptosis. The anticancer effect was related to reactive oxygen species (ROS) accumulation and could be reversed by ROS scavengers, catalase and N-acetyl-l-cysteine. Curcumin decreased mitochondrial transmembrane potential and induced ROS production, thereby activating the DNA damage/repair pathway and mitochondrial apoptosis.

Conclusion: These results indicate that curcumin could be an effective therapeutic candidate for NSCLC.

Keywords: DNA damage; ER stress; curcumin; mitochondrial apoptosis; non-small-cell lung cancer; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Curcumin / pharmacology*
  • DNA Damage / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Curcumin