The Synergistic Effect of Piperlongumine and Sanguinarine on the Non-Small Lung Cancer

Molecules. 2020 Jul 3;25(13):3045. doi: 10.3390/molecules25133045.

Abstract

Background: Cancers are one of the leading causes of deaths nowadays. The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine. Therefore, the evaluation of the influence of two alkaloids-piperlongumine (PL), sanguinarine (SAN) and their combination-on the basic life processes of the A549 cell line was considered reasonable.

Methods: The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death, changes in the distribution of cell cycle phases, reorganization of cytoskeleton and metastatic potential of A549 cells. The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines: MCF-7, H1299 and HepG2.

Results: The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells. Additionally, the compounds and their combination did not exhibit a cytotoxic effect against normal cells. The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition.

Conclusion: Selected alkaloids exhibit a cytotoxic effect on A549 cells. In turn, treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species (ROS).

Keywords: cell death; combination therapy; lung cancer; piperlongumine; sanguinarine.

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Apoptosis
  • Benzophenanthridines / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Dioxolanes / pharmacology*
  • Drug Synergism*
  • Humans
  • Isoquinolines / pharmacology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Neoplasm Invasiveness
  • Reactive Oxygen Species / metabolism
  • Tumor Cells, Cultured

Substances

  • Anti-Infective Agents
  • Benzophenanthridines
  • Dioxolanes
  • Isoquinolines
  • Reactive Oxygen Species
  • sanguinarine
  • piperlongumine