HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells |
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| Authors: | Narissara Namwan Gulsiri Senawong Chanokbhorn Phaosiri Pakit Kumboonma La-or Somsakeesit Arunta Samankul Chadaporn Leerat Thanaset Senawong |
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| Institution: | 1.Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand; (N.N.); (G.S.); (A.S.); (C.L.);2.Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand;3.Department of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima 30000, Thailand;4.Department of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan, Khon Kaen 40000, Thailand; |
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| 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. |
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| Keywords: | apoptosis cell cycle arrest curcumin derivative HDAC inhibitor lung cancer molecular docking |
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