title: [Inducing effect of chidamide on apoptosis of multiple myeloma cells and its relerance to DNA damage response].
abstract: OBJECTIVE
  This study was aimed to explore the effect of a novel histone deacetylase inhibitor Chidamide on apoptosis of human multiple myeloma(MM) cells and its relevance to DNA damage response(DDR).
  
  
  METHODS
  The cell proliferation was detected by MTT method, apoptosis and cell cycle distribution were analyzed by flow cytometry, the expression levels of targeted proteins were detected by Western blot, the DNA damage response was blocked by ATM kinase inhibitor KU-55933.
  
  
  RESULTS
  Chidamide inhibited RPMI 8226 cell proliferation in dose- and time-dependent manner and its IC50 values of 24,48,72 h were 9.6, 6 and 2.8 µmol/L respectively. Chidamide induced cell cycle arrest of RPMI 8226 cells in G0/G1 phase by upregulating the expression of P21. Chidamide triggered caspase-3 dependent apoptosis and upregulated expression of DDR-related proteins including γH2AX, pATM in RPMI 8226 cells. Pretreatment with ATM kinase inhibitor KU-55933 down-regulated expression of DDR related proteins induced by chidamide, thereby inhibiting DNA damage response and finally resulting in suppression of apoptotic cell death.
  
  
  CONCLUSIONS
  Proliferative inhibtion, cell cycle arrest and apoptosis of multiple myeloma cells induced by chidamide involve DDR.
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Tang
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xin
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. E-mail: gaoguangxun@fmmu.edu.cn.
authors.forename: Guang-Xun
authors.initials: GX
authors.lastname: Gao
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. E-mail: 13709220311@126.com.
authors.forename: Mi-Mi
authors.initials: MM
authors.lastname: Shu
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. E-mail: xiequnchen@fmmu.edu.cn.
authors.forename: Xie-Qun
authors.initials: XQ
authors.lastname: Chen
mesh_terms: D000631:Aminopyridines; D017209:Apoptosis; D001549:Benzamides; D053148:Caspase 3; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D015536:Down-Regulation; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009025:Morpholines; D009101:Multiple Myeloma; D011753:Pyrones
chemical_list: C495818:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one; D000631:Aminopyridines; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D009025:Morpholines; D011753:Pyrones; C547816:N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; C505407:CASP3 protein, human; D053148:Caspase 3