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.