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  • Title: Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species.
    Author: Zhang J, Wu D, Vikash, Song J, Wang J, Yi J, Dong W.
    Journal: Dig Dis Sci; 2015 Oct; 60(10):2985-95. PubMed ID: 25972151.
    Abstract:
    BACKGROUND: Hesperetin, has been shown to exert biological activities on various types of human cancers. However, few related studies on gastric cancer are available. AIM: In this study, we sought to investigate the effect of hesperetin on gastric cancer and clarify its specific mechanism. MATERIALS AND METHODS: Cell Counting Kit-8, 2',7'-dichlorofluorescin diacetate, JC-1, Hoechst 33258 staining, and western bolt were used to detect cell viability, levels of intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (△ψ m), cell apoptosis, and expressions of mitochondrial pathway proteins, respectively. Meanwhile, xenograft tumor models in nude mice were made to evaluate the effect of hesperetin on gastric cancer in vivo. RESULTS: Compared with the control group, the proliferation of gastric cancer cells in hesperetin groups was significantly inhibited (P < 0.05), and dose- and time-dependent effects were observed. Pretreatment with H2O2 (1 mM) or N-acetyl-L-cysteine (5 mM) enhanced or attenuated the hesperetin-induced inhibition of cell viability (P < 0.05). Percentages of apoptotic cells, levels of intracellular ROS, and △ψ m varied with the dose and treatment time of hesperetin (P < 0.05), and hesperetin caused an increase in the levels of AIF, Apaf-1, Cyt C, caspase-3, caspase-9, and Bax and a decrease in Bcl-2 levels (P < 0.05). Meanwhile, hesperetin significantly inhibited the growth of xenograft tumors (P < 0.05). CONCLUSION: Our study suggests that hesperetin could inhibit the proliferation and induce the apoptosis of gastric cancer cells via activating the mitochondrial pathway by increasing the ROS.
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