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Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species

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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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Authors and Affiliations

  1. Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China

    Jixiang Zhang, Dandan Wu,  Vikash, Jia Song, Jing Wang, Jiasheng Yi & Weiguo Dong

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  1. Jixiang Zhang
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  2. Dandan Wu
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  3. Vikash
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  6. Jiasheng Yi
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  7. Weiguo Dong
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Correspondence to Weiguo Dong.

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Zhang, J., Wu, D., Vikash et al. Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species. Dig Dis Sci 60, 2985–2995 (2015). https://doi.org/10.1007/s10620-015-3696-7

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  • DOI: https://doi.org/10.1007/s10620-015-3696-7

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