| Abstract |
Previous research reported that the curcumin derivative (CU17) inhibited several cancer
cell growths in vitro. However, its anticancer potential against human lung cancer cells (A549
cell lines) has not yet been evaluated. The purpose of this research was to examine the HDAC
inhibitory and anti-cancer activities of CU17 compared to curcumin (CU) in A549 cells. An in vitro
study showed that CU17 had greater HDAC inhibitory activity than CU. CU17 inhibited HDAC
activity in a dose dependent manner with the half-maximal inhibitory concentration (IC50) value of
0.30 ± 0.086 µg/mL against HDAC enzymes from HeLa nuclear extract. In addition, CU17 could
bind at the active pockets of both human class I HDACs (HDAC1, 2, 3, and 8) and class II HDACs
(HDAC4, 6, and 7) demonstrated by molecular docking studies, and caused hyperacetylation of
histone H3 (Ac-H3) in A549 cells shown by Western blot analysis. MTT assay indicated that both CU
and CU17 suppressed A549 cell growth in a dose- and time-dependent manner. Besides, CU and
CU17 induced G2/M phase cell cycle arrest and p53-independent apoptosis in A549 cells. Both CU
and CU17 down-regulated the expression of p53, p21, Bcl-2, and pERK1/2, but up-regulated Bax
expression in this cell line. Although CU17 inhibited the growth of lung cancer cells less effectively
than CU, it showed less toxicity than CU for non-cancer cells. Accordingly, CU17 is a promising
agent for lung cancer treatment. Additionally, CU17 synergized the antiproliferative activity of Gem
in A549 cells, indicating the possibility of employing CU17 as an adjuvant treatment to enhance the
chemotherapeutic effect of Gem in lung cancer. |
Publication
Journal Publication
ไทย