title: Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation.
abstract: BACKGROUND
  Curcumin induces apoptosis and autophagy in different cancer cells. Moreover, chemical and biological experiments have evidenced that curcumin is a biologically active iron chelator and induces cytotoxicity through iron chelation. We thus hypothesized that curcumin may induce apoptosis and autophagy in castration-resistant prostate cancer (CRPC) cells through its iron-chelating properties.
  
  
  METHODS
  CRPC cells were loaded with curcumin alone or in combination with ferric ammonium citrate (FAC). Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and caspase activity. Autophagy status was analyzed by the detection of autophagosomes and light chain 3-II (LC3-II) using transmission electron microscopy and Western blot. Iron-binding activity of curcumin was assessed by spectrophotometry and MTT assay. The expression levels of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) were examined by Western blot.
  
  
  RESULTS
  Curcumin induced apoptosis and autophagy in CRPC cells. Combining curcumin with autophagy inhibitors (3-methyladenine [3-MA]) synergized the apoptotic effect of curcumin. Moreover, curcumin bound to FAC at a ratio of ~1:1, as assessed by spectrophotometry and MTT assay. Apoptosis and autophagy induced by curcumin were counteracted by equal amounts of FAC. At apoptosis- and autophagy-inducing concentrations, curcumin enhanced the expression levels of TfR1 and IRP1, indicative of iron deprivation induced by curcumin.
  
  
  CONCLUSIONS
  Together, our results indicate that curcumin induces apoptosis and protective autophagy in CRPC cells, which are at least partially dependent on its iron-chelating properties.
authors.affiliation: Department of Urology, Tongji Hospital.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Urology, Tongji Hospital.
authors.forename: Xueyou
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Urology, Tongji Hospital.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital.
authors.forename: Xing
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Urology, Tongji Hospital.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D007502:Iron Chelating Agents; D003474:Curcumin
keywords: apoptosis; autophagy; castration-resistant prostate cancer; curcumin; iron chelation