Cyclooxygenase-2 knockdown using retinoic acid chalcone (RAC), a promising therapeutic strategy for colon cancer.
Retinoic acid is an effective agent in the treatment of epithelial and hematological malignancies. The present study demonstrates that retinoic acid chalcone (RAC), an analogue of retinoic acid inhibits cell proliferation and induces apoptosis in HCT-15 and CT26.WT colon cancer cell lines. In HCT-15 cells the percentage of apoptotic cells increased from 32.4 ± 3, 45.0 ± 3 to 72.6 ± 5% respectively at 10, 15 and 20 μg/mL compared to 3.7% in control. Similarly in CT26.WT cells the percentage increased from 28.6 ± 3, 41.2 ± 3 to 65.4 ± 5% on treatment with 10, 15 and 20 μg/mL concentrations of RAC after 72 h compared to 2.9 ± 1% in control. Western blotting, fluorescence-activated cell sorting analysis and reverse transcription-PCR assays were used to investigate these effects. RAC inhibited the overexpression of COX-2, PGE2 and PGE2 receptor (EP1 and EP4) in the colon cancer cell lines. RAC mediated inhibition of cell growth and induction of apoptosis through COX-2 inhibition was also confirmed by treating the HCT-15 and CT26.WT colon cancer cells with COX-2 inhibitor, indomethacin and transfection of cells with COX-2 small interfering RNA. In nude mice with tumor xenografts, treatment with RAC-supplemented diet caused inhibition of COX-2, PGE2, and PGE2 receptors (EP1, EP3, and EP4) in tumors. Thus RAC can be a potential candidate for the treatment of colon cancer through the inhibition of COX-2 expression and subsequent inhibition of PGE2 and PGE2 receptors.
Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Chao
C
Jiang
Department of Pharmacology, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Qiong
Q
Wang
Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Zhe
Z
Xu
Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Wei-Su
WS
Li
Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Che
C
Chen
Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Xue-Quan
XQ
Yao
Department of Digestive Tumor Surgery, Affiliated Hospital of Nanjing University of TCM Nanjing 210029, China.
Fu-Kun
FK
Liu
Cell proliferation; apoptosis; indomethacin; inhibition; transfection