Trichostatin A improves the anticancer activity of low concentrations of curcumin in human leukemia cells

Curcumin (Cur), a promising anticancer drug, kills tumor cells through either diminishing or promoting reactive oxygen species (ROS) generation. In this study, it was investigated whether trichostatin A (TSA), a specific histone deacetylase (HDAC) inhibitor and a new anticancer drug, could improve t...

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Veröffentlicht in:Pharmazie 2006-08, Vol.61 (8), p.710-716
Hauptverfasser: Chen, Jie, Bai, Hai, Wang, Cunbang, Kang, Jiuhong
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container_end_page 716
container_issue 8
container_start_page 710
container_title Pharmazie
container_volume 61
creator Chen, Jie
Bai, Hai
Wang, Cunbang
Kang, Jiuhong
description Curcumin (Cur), a promising anticancer drug, kills tumor cells through either diminishing or promoting reactive oxygen species (ROS) generation. In this study, it was investigated whether trichostatin A (TSA), a specific histone deacetylase (HDAC) inhibitor and a new anticancer drug, could improve the anticancer activity of low concentrations of Cur in human leukemia cells (HL-60). HL-60 cells were treated with Cur, TSA or their combinations; cell proliferation arrest, lactate dehydrogenase (LDH) release and cell viability were measured as indicators of cell damage. Reactive oxygen species (ROS) accumulation and the acetylation of histones were also measured. The cytotoxicity of Cur and TSA increased in a time and dose-dependent manner. Low Cur (no more than 20 μM) diminished the ROS generation in HL-60 cells, while high Cur (50 and 100 μM) promoted that. In contrast, TSA showed no influence on ROS generation. When their effects on histone acetylation were determined, low Cur showed no effect, while TSA significantly increased that. As expected, combinations of low Cur and TSA could not only diminish ROS generation, but also increase histone acetylation, and hence showed a more significant cytotoxicity in HL-60 cells. Since the extra ROS generation may also harm normal cells, instead of using high Cur, combining low Cur with TSA is obviously a better strategy to improve the anticancer activity of Cur.
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In this study, it was investigated whether trichostatin A (TSA), a specific histone deacetylase (HDAC) inhibitor and a new anticancer drug, could improve the anticancer activity of low concentrations of Cur in human leukemia cells (HL-60). HL-60 cells were treated with Cur, TSA or their combinations; cell proliferation arrest, lactate dehydrogenase (LDH) release and cell viability were measured as indicators of cell damage. Reactive oxygen species (ROS) accumulation and the acetylation of histones were also measured. The cytotoxicity of Cur and TSA increased in a time and dose-dependent manner. Low Cur (no more than 20 μM) diminished the ROS generation in HL-60 cells, while high Cur (50 and 100 μM) promoted that. In contrast, TSA showed no influence on ROS generation. When their effects on histone acetylation were determined, low Cur showed no effect, while TSA significantly increased that. As expected, combinations of low Cur and TSA could not only diminish ROS generation, but also increase histone acetylation, and hence showed a more significant cytotoxicity in HL-60 cells. 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In this study, it was investigated whether trichostatin A (TSA), a specific histone deacetylase (HDAC) inhibitor and a new anticancer drug, could improve the anticancer activity of low concentrations of Cur in human leukemia cells (HL-60). HL-60 cells were treated with Cur, TSA or their combinations; cell proliferation arrest, lactate dehydrogenase (LDH) release and cell viability were measured as indicators of cell damage. Reactive oxygen species (ROS) accumulation and the acetylation of histones were also measured. The cytotoxicity of Cur and TSA increased in a time and dose-dependent manner. Low Cur (no more than 20 μM) diminished the ROS generation in HL-60 cells, while high Cur (50 and 100 μM) promoted that. In contrast, TSA showed no influence on ROS generation. When their effects on histone acetylation were determined, low Cur showed no effect, while TSA significantly increased that. As expected, combinations of low Cur and TSA could not only diminish ROS generation, but also increase histone acetylation, and hence showed a more significant cytotoxicity in HL-60 cells. Since the extra ROS generation may also harm normal cells, instead of using high Cur, combining low Cur with TSA is obviously a better strategy to improve the anticancer activity of Cur.</abstract><cop>Germany</cop><pub>Govi-Verlag</pub><pmid>16964716</pmid><tpages>7</tpages></addata></record>
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subjects Acetylation
Acetylcysteine - pharmacology
Antineoplastic Agents, Phytogenic - pharmacology
Antioxidants - pharmacology
Ascorbic Acid - pharmacology
Cell Line, Tumor
Cell Proliferation
Cell Survival - drug effects
Curcumin - pharmacology
Drug Synergism
Histones - isolation & purification
Histones - metabolism
HL-60 Cells
Humans
Hydroxamic Acids - pharmacology
Indicators and Reagents
L-Lactate Dehydrogenase - metabolism
Leukemia, Promyelocytic, Acute - drug therapy
Protein Synthesis Inhibitors - pharmacology
Reactive Oxygen Species - metabolism
title Trichostatin A improves the anticancer activity of low concentrations of curcumin in human leukemia cells
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