|
Chen J, Bai H, Wang C, Kang J.
Trichostatin A improves the anticancer activity of low
concentrations of curcumin in human leukemia cells.
Pharmazie. 2006 Aug;61(8):710-6.
Hematological Center of PLA, Department of Hematology,
General Hospital of Lanzhou, Lanzhou, China.
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, 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, trichostatin A 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 trichostatin A 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, trichostatin A showed no influence
on ROS generation. When their effects on histone acetylation
were determined, low Cur showed no effect, while trichostatin A
significantly increased that. As expected, combinations of low
Cur and trichostatin A 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 trichostatin A is obviously a better
strategy to improve the anticancer activity of Cur.
PMID: 16964716
|
