Abstract
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.
Highlights
Cancer is considered the second leading cause of death worldwide accounting for an estimated 18.1 million new cancer cases with around 9.6 million cancer deaths in 2018 (Bray et al, 2018)
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
For full length Poly (ADP-ribose) polymerase-1 (PARP-1) and full-length caspase 3 and B-cell lymphoma 2 (Bcl-2) proteins the results showed a significant decrease in their expression in A549 cells treated with C. aronia L. for 48 hr (Figure 7A, B)
Summary
Cancer is considered the second leading cause of death worldwide accounting for an estimated 18.1 million new cancer cases with around 9.6 million cancer deaths in 2018 (Bray et al, 2018). It is estimated that cancer-related deaths would increase to over 17 million in 2030 (Thun et al, 2009). Lung cancer is considered a major cause of cancer diagnosis (11.6% of the total cases) and deaths (18.4% of cancer deaths) in both sexes combined (Bray et al, 2018). NSCLC is divided into 3 major subtypes: squamous cell carcinoma, adenocarcinoma and large cell carcinoma. It accounts for 75 % of all lung cancer cases
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