title: Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species.
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.
  
  
  OBJECTIVE
  In this study, we sought to investigate the effect of hesperetin on gastric cancer and clarify its specific mechanism.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China. zhangjixiang_1986@126.com.
authors.forename: Jixiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.lastname: Vikash
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China. dwg@whu.edu.cn.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Dong
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006569:Hesperidin / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D017382:Reactive Oxygen Species; D006569:Hesperidin; C013015:hesperetin
keywords: Apoptosis; Gastric cancer; Hesperetin; Mitochondria; Reactive oxygen species