Anticancer Effects of Hesperidin on Gastric Cancer Cell Lines and Fibroblast Cell Lines by Reducing the Activation of PI3K Pathway

Background: Cancer is one of the leading causes of death worldwide. In recent years, the need to pay attention to medicinal plants has increased due to the side effects of drugs and drug treatment. Hesperidin has medicinal uses in traditional medicine and is used as an antidote for therapeutic diseases. This study was conducted to investigate the toxicity effect of Hesperidin on gastric cancer cell lines (AGS) and normal fibroblast cell lines (SKM). Methods: Hesperidin plant extract with different types (100, 50, 10, and 50 μg/mL) was released on AGS and SKM cell lines for 24 hours by MTT test. The amount of apoptosis induction was evaluated by flow cytometry with Annexin V/PI staining and changes in the expression of genes (BAX and BCL-2) by real-time polymerase chain reaction. The effect of the drug on phosphoinositide 3-kinases (PI3K) was determined by the Western blot technique. The data were analyzed by SPSS statistical software using a one-way variance test and Tukey’s test (P<005). Results: Hesperidin had a cytotoxic effect on SKM and AGS cell lines and induced apoptosis. In the treatment with Hesperidin (100 μg/mL) for 24 hours, gene expression decreased in AGS and SKM and increased in BCL2 and BAX, (P<005). The growth rate of PI3K was decreased by the effect of the drug. Conclusion: Hesperidin, with a specific effect on SKM and AGS cancer cells, has the ability to grow these cells at a dose of 100 micrograms per milliliter.