Li Xu1, Hai-Long Tang1, Xue Gong1, Xiao-Li Xin1, Ying Dong1, Guang-Xun Gao2, Mi-Mi Shu3, Xie-Qun Chen4. 1. Department of Hematology, Xijing Hospital, Fourth Military Medical University; Hematologic Disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. 2. 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. 3. 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. 4. 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.
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. CONCLUSION: Proliferative inhibtion, cell cycle arrest and apoptosis of multiple myeloma cells induced by chidamide involve DDR.
OBJECTIVE: This study was aimed to explore the effect of a novel histone deacetylase inhibitor Chidamide on apoptosis of humanmultiple 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. CONCLUSION: Proliferative inhibtion, cell cycle arrest and apoptosis of multiple myeloma cells induced by chidamide involve DDR.