Synergistic antitumor effect of histone deacetylase inhibitor and Doxorubicin in peripheral T-cell lymphoma.
Chidamide (CS055) is a new and highly selective histone deacetylase inhibitor displaying significant single-agent activity in peripheral T-cell lymphoma (PTCL). But there is little known the synergistic effect between CS055 and chemotherapy. The purpose of this study is to explore the synergistic effect and molecular mechanisms of CS055 combination with Doxorubicin in PTCL cells. We found that CS055 showed dose- and time-dependent inhibition effects on PTCL cell. Meanwhile, the synergistic effect was significantly observed after combination treatment with lower drug-concentration of CS055 and Doxorubicin. Lower drug-concentration of CS055 induced weak apoptosis in PTCL cells, but combination treatment with CS055 and Doxorubicin promoted more significant apoptosis. Combination treatment with CS055 and Doxorubicin significantly changed mitochondrial membrane potential and H3 acetylated level, resulting in up-regulating DNA damage protein p-γH2AX and apoptosis proteins including cleaved-caspase-3, cleaved-caspase-9 and cleaved-PARP, and down-regulating anti-apoptosis protein Bcl-2. In a word, Doxorubicin could increase the CS055-induced inhibition effects on PTCL cells, suggesting that CS055 combination with Doxorubicin or Doxorubicin-based chemotherapy drugs might be a new therapy approach for PTCL patients.
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. Electronic address: zhlwgq@126.com.
Huilai
H
Zhang
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Geratology, The First Affiliated Hospital of Zhengzhou University, China.
Ling
L
Dong
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Oncology, The First People's Hospital of Xiangyang, Hubei, China.
Qingqing
Q
Chen
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Lingzhe
L
Kong
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Bin
B
Meng
Department of Oncology, Tianjin Union Medicine Center, Tianjin, China.
Huaqing
H
Wang
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Department of Pathology and Microbiology and Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Kai
K
Fu
Department of Cellular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Xi
X
Wang
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China; Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Sweden.
Qiang
Q
Pan-Hammarström
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Ping
P
Wang
Department of Lymphoma, Department of Pathology and Department of Radiotherapy, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. Electronic address: tjzlyy_xianhuow@163.com.
Xianhuo
X
Wang
D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006657:Histones / Q000378:metabolism; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000631:Aminopyridines; D051017:Apoptosis Regulatory Proteins; D001549:Benzamides; C468783:H2AX protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D004317:Doxorubicin; C547816:N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
Chidamide; Doxorubicin; PTCL; Synergistic antitumor effect