title: Histone deacetylase inhibitor, Romidepsin (FK228) inhibits endometrial cancer cell growth through augmentation of p53-p21 pathway.
abstract: OBJECTIVE
  Romidepsin (FK228), a Histone Deacetylase (HDAC) inhibitor, has been used for anti-cancer therapies. However, the anti-cancer effect of FK228 and its underlying mechanism in endometrial carcinoma (EC) have not been studied. The aime of this study was to investigate the anti-cancer effects of FK228 and the associated mechanism(s) in EC.
  
  
  METHODS
  Ishikawa and HEC-1-A endometrial cancer cells were treated with 8nM concentration of FK228 and cell growth was measured by XTT assay. The cell cycle distribution and cell death were measured by flow cytometry, immunofluorescence, respectively. The mNRA and protein expressions were analyzed by quantitative RT-PCR and western blot, respectively.
  
  
  RESULTS
  Based on assays carried out in EC cell lines, it was observed that FK228 inhibited EC cell proliferation in a dose and time-dependent manner. Furthermore, following treatment with FK228 for 48h, there were significant induction of apoptosis and cell cycle arrest at G0/G1 phase in EC cells. Moreover, FK228 treatment significantly increased the mRNA and protein expressions of p53, p21, cleaved caspases such as 3, 7 and 8 and PARP. Further, FK228 treatment increased the levels of acetylated histone H3 and H4 that confirms the HDAC inhibition.
  
  
  CONCLUSIONS
  In conclusion, FK228 inhibits EC tumor cell proliferation and induces apoptosis by activation caspase/PARP via the induction of p53/p21 signaling cascades, suggesting that FK228 is a potential therapeutic agent for EC.
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Fujian Medical College, China. Electronic address: liluhong@hotmail.com.
authors.forename: Lu-Hong
authors.initials: LH
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Fujian Medical College, China.
authors.forename: Pei-Ru
authors.initials: PR
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Fujian Medical College, China.
authors.forename: Pei-Ya
authors.initials: PY
authors.lastname: Cai
authors.affiliation: Department of Radiology, Second Affiliated Hospital of Fujian Medical College, China.
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Li
mesh_terms: D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D005260:Female; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C087123:romidepsin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: Apoptosis; Cell-cycle and p53; Endometrial cancer; FK228