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 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 microM) diminished the ROS generation in HL-60 cells, while high Cur (50 and 100 microM) 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.
Chen
Jie
J
Hematological Center of PLA, Department of Hematology, General Hospital of Lanzhou, Lanzhou, China.
Bai
Hai
H
Wang
Cunbang
C
Kang
Jiuhong
J
D000107:Acetylation; D000111:Acetylcysteine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D018922:HL-60 Cells; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D006657:Histones; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; C012589:trichostatin A; D007770:L-Lactate Dehydrogenase; D003474:Curcumin; D001205:Ascorbic Acid; D000111:Acetylcysteine