title: Catechins induced acute promyelocytic leukemia cell apoptosis and triggered PML-RARα oncoprotein degradation.
abstract: BACKGROUND
  It has recently been reported that the extracts of green tea polyphenol have cancer preventive effects. In this study, we investigated the effect of the natural composition from green tea leaves Catechins on acute promyelocytic leukemia (APL).
  
  
  METHODS
  In vitro, APL cell lines NB4, retinoic acid-resistant NB4-R1 and NB4-R2 were treated with different concentrations of Catechins. Cell viability and cell apoptosis were analyzed using MTT assay and flow cytometric assay, respectively. Expression of proteins related to apoptosis and PML-RARα oncoprotein were assessed by Western blot. In vivo anti-tumor activity of Catechins was examined in nude mice xenografted with NB4 cells and in situ cell apoptosis was detected by terminal deoxytransferase-catalyzed DNA nick-end labeling assay.
  
  
  RESULTS
  Catechins at micromolar concentration levels significantly inhibited APL cell proliferation and induced cell apoptosis, in association with mitochondria damage, ROS production and caspase activation. The anti-apoptotic Bcl-2 family member Bcl-xL was down regulated, with pro-apoptotic member Bax remaining unchanged. Moreover, Catechins induced the degradation of PML-RARα oncoprotein. Catechins-mediated apoptotic effect was also observed in primary APL cells without affecting normal hematopoietic progenitor cells. In the murine xenograft model, Catechins remarkably inhibited tumor growth and induced in situ leukemic cell apoptosis.
  
  
  CONCLUSIONS
  Catechins might be a potential candidate for APL treatment by activating intrinsic apoptotic pathway and targeting PML-RARα oncoprotein.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Qiu-Sheng
authors.initials: QS
authors.lastname: Chen
authors.forename: Peng-Peng
authors.initials: PP
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Qian
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Sheng
authors.forename: Xiang-Qin
authors.initials: XQ
authors.lastname: Wen
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002392:Catechin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015514:Oncogene Proteins, Fusion / Q000187:drug effects* / Q000378:metabolism; D013662:Tea; D023041:Xenograft Model Antitumor Assays
chemical_list: D015514:Oncogene Proteins, Fusion; D013662:Tea; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D002392:Catechin