title: Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner.
abstract: OBJECTIVE
  This study aims to evaluate the anti-cancer effect of daucosterol and explore its possible mechanism.
  
  
  METHODS
  MTT and colony formation assay were performed to determine the effect of daucosterol on cancer cell proliferation in vitro. H22 allograft model was used for the assessment of its anti-cancer activity in vivo. Intracellular generation of reactive oxygen species (ROS) was measured using DCFH-DA probe with flow cytometry system and a laser scanning confocal microscope. LC3 (microtubule-associated protein 1 light chain 3)-II conversion was monitored with immunofluorescence and immunoblotting to demonstrate daucosterol-induced autophagy.
  
  
  RESULTS
  We found that daucosterol inhibits the proliferation of human breast cancer cell line MCF-7 and gastric cancer cell lines MGC803, BGC823 and AGS in a dose-dependent manner. Furthermore, daucosterol inhibits murine hepatoma H22 cell growth in ICR mice. Daucosterol treatment induces intracellular ROS generation and autophagy, but not apoptotic cell death. Treatment with ROS scavenger GSH (reduced glutathione), NAC (N-acetyl-l-cysteine) or autophagy inhibitor 3-Methyladenine (3-MA) counteracted daucosterol-induced autophagy and growth inhibition in BGC823 and MCF-7 cancer cells.
  
  
  CONCLUSIONS
  Daucosterol inhibits cancer cell proliferation by inducing autophagy through ROS-dependent manner and could be potentially developed as an anti-cancer agent.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Chuanke
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: She
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Su
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing, China.
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Cai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing, China. Electronic address: scc@bjcancer.org.
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012855:Sitosterols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012855:Sitosterols; C025946:3-methyladenine; D005978:Glutathione; D000225:Adenine; C011015:lyoniside; D000111:Acetylcysteine
keywords: Autophagy; Cancer; Daucosterol; ROS