Histone deacetylases 1 and 2 cooperate in regulating BRCA1, CHK1, and RAD51 expression in acute myeloid leukemia cells. 2017

Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
National Engineering Laboratory for AIDS Vaccine and Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, P. R. China.

Resistance to chemotherapy and a high relapse rate highlight the importance of finding new therapeutic options for the treatment of acute myeloid leukemia (AML). Histone deacetylase (HDAC) inhibitors (HDACIs) are a promising class of drugs for the treatment of AML. HDACIs have limited single-agent clinical activities, but when combined with conventional or investigational drugs they have demonstrated favorable outcomes. Previous studies have shown that decreasing expression of important DNA damage repair proteins enhances standard chemotherapy drugs. In our recent studies, the pan-HDACI panobinostat has been shown to enhance conventional chemotherapy drugs cytarabine and daunorubicin in AML cells by decreasing the expression of BRCA1, CHK1, and RAD51. In this study, we utilized class- and isoform-specific HDACIs and shRNA knockdown of individual HDACs to determine which HDACs are responsible for decreased expression of BRCA1, CHK1, and RAD51 following pan-HDACI treatment in AML cells. We found that inhibition of both HDAC1 and HDAC2 was necessary to decrease the expression of BRCA1, CHK1, and RAD51, enhance cytarabine- or daunorubicin-induced DNA damage and apoptosis, and abrogate cytarabine- or daunorubicin-induced cell cycle checkpoint activation in AML cells. These findings may aid in the development of rationally designed drug combinations for the treatment of AML.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D003561 Cytarabine A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472) Ara-C,Arabinofuranosylcytosine,Arabinosylcytosine,Cytosine Arabinoside,Aracytidine,Aracytine,Cytarabine Hydrochloride,Cytonal,Cytosar,Cytosar-U,beta-Ara C,Ara C,Arabinoside, Cytosine,Cytosar U,beta Ara C
D003630 Daunorubicin A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS. Daunomycin,Rubidomycin,Rubomycin,Cerubidine,Dauno-Rubidomycine,Daunoblastin,Daunoblastine,Daunorubicin Hydrochloride,NSC-82151,Dauno Rubidomycine,Hydrochloride, Daunorubicin,NSC 82151,NSC82151
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006877 Hydroxamic Acids A class of weak acids with the general formula R-CONHOH. Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000071877 Checkpoint Kinase 1 A serine/threonine-specific protein kinase which is encoded by the CHEK1 gene in humans. Checkpoint kinase 1 (also known as Chk1) coordinates DNA damage response and cell cycle checkpoint response. Under these conditions, activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death, to prevent damaged cells from progressing through the cell cycle. Checkpoint-1 Kinase,Chk1 Kinase,Chk1 Protein Kinase,Protein Kinase, Chk1
D000074084 THP-1 Cells A human leukemia monocytic cell line derived from a patient with LEUKEMIA, MONOCYTIC, ACUTE. It is used as a model to study the function of MONOCYTES and MACROPHAGES, their signaling pathways, nutrient and drug transport. THP-1 Cell Line,Cell Line, THP-1,Cell Lines, THP-1,Cell, THP-1,Cells, THP-1,THP 1 Cell Line,THP 1 Cells,THP-1 Cell,THP-1 Cell Lines

Related Publications

Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
January 2017, PloS one,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
February 2011, PloS one,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
January 2021, Frontiers in oncology,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
June 2021, Sheng li xue bao : [Acta physiologica Sinica],
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
January 1998, Journal of cellular biochemistry,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
January 1998, Journal of cellular biochemistry. Supplement,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
January 2013, PloS one,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
October 2003, EMBO reports,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
April 2013, Oncogene,
Jianyun Zhao, and Chengzhi Xie, and Holly Edwards, and Guan Wang, and Jeffrey W Taub, and Yubin Ge
March 2014, BMC clinical pathology,
Copied contents to your clipboard!