Anti-Oxidant, Anti-Hemolytic Effects of Crataegus aronia Leaves and Its Anti- Proliferative Effect Enhance Cisplatin Cytotoxicity in A549 Human Lung Cancer Cell Line

Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2993-3003. doi: 10.31557/APJCP.2020.21.10.2993.


Objective: For Arabian traditional medicine, Crataegus aronia syn. Azarolus (L) Bosc. ex DC (Rosaceae) is widely used to treat diabetes, sexual weakness, cardiovascular diseases and cancer. The anti-cancerous and anti-hemolysis effects of the hydroalcoholic extract of this plant have never been investigated before. The present study aims to evaluate the biological activities of the hydroalcoholic extract of Crataegus aronia leaves in combination with cisplatin, one of the most widely employed chemotherapeutics, on A549 human lung cancer cell line.

Methods: The anti-oxidant and anti-proliferative activities of leaves, fruits, seeds of C. aronia were investigated by DPPH method and MTT assay; respectively. Cell migration activity was investigated by wound healing and by cell aggregation assays. The effect of C. aronia in inducing cell cycle arrest along with activating cell apoptosis was evaluated by flow cytometry and Western blot assays, respectively.

Results: Our results showed that C. aronia leaves (C. aronia L.) had the highest anti-oxidant and anti-proliferative activities. The leaves extract was potent against hemolysis of the human erythrocytes and showed elevated decrease in migration by reducing wound healing migration and by increasing cell aggregation. Finally, C. aronia L. treatment exhibited apoptotic activity on A549 cells by the down-regulation of PARP-1, caspase-3 and Bcl-2 proteins and by increasing the percentage of A549 cells in sub G0 cell cycle. Moreover, the co-treatment of C. aronia L. and cisplatin remarkably sensitised A549 cells to cisplatin.

Conclusion: The results suggested that C. aronia L. could be used as a potential treatment against human lung cancer exhibiting minimal side effects on human health.<br />.

Keywords: Apoptosis; Cell Arrest Cycle; Cells aggregation; Keywords: Cells Migration.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / pharmacology
  • Antioxidants / pharmacology*
  • Apoptosis
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation*
  • Cisplatin / pharmacology*
  • Crataegus
  • Drug Synergism
  • Hemolysis / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*


  • Antineoplastic Agents
  • Antioxidants
  • Plant Extracts
  • crataegus extract
  • Cisplatin