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Article

A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth

  • Authors:
    • Kong-Wang Hu
    • Xiao-Hua Pan
    • Fei-Hu Chen
    • Rong Qin
    • Li-Ming Wu
    • Hua-Gang Zhu
    • Fan-Rong Wu
    • Jin-Fang Ge
    • Wen-Xiu Han
    • Chun-Lin Yin
    • Hong-Jun Li
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Gynaecology and Obstetrics, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Pathology, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Radiotherapy, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
  • Pages: 415-422
    |
    Published online on: December 4, 2013
       https://doi.org/10.3892/ijmm.2013.1574
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Abstract

Retinoic acid (RA) analogs have been used in the treatment of a variety of cancers; however, their application is limited due to serious therapy-related sequelae. In the present study, the effects of a novel RA analog, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), on the growth of gastric cancer cells were evaluated. Three gastric cancer cell lines, AGS, MKN-74 and SC-M1, were treated with either all‑trans retinoic acid (ATRA) or ATPR, and their growth and distribution in different cell cycle phases were assessed using an MTT assay and propidium iodide (PI) staining followed by flow cytometry. The binding affinity of ATPR to the retinoic acid receptors, retinoic acid receptor-α (RAR-α) and retinoid X receptor-α (RXR-α), was determined using ligand-binding assays. Activator protein-1 (AP-1) activity was measured using a luciferase reporter assay. Western blot analysis was used to determine cyclin E, Bcl-2 and Bax protein expression. ATPR preferentially bound RXR-α (0.04 nM) as compared with RAR-α (20.96 nM). Although both ATRA and ATPR inhibited the growth of AGS, MKN-74 and SC-M1 cells in a dose-dependent manner, a significantly greater inhibitory effect was observed with treatment with 5 and 500 µM ATPR for 3 days (P<0.05). In addition, ATPR (50 µM), but not ATRA, significantly increased the population of AGS and MKN-74 cells in the subG1 phase and decreased the Bcl-2/Bax ratio (P<0.05). Furthermore, in MNK-74 and SC-M1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) and 5 or 10 µM of ATPR significantly suppressed the activity of the AP-1 reporter as compared to treatment with ATRA (P<0.05). Thus, ATPR inhibits cancer cell proliferation to a greater extent compared to ATRA, possibly through the RXR-mediated inhibition of AP-1 activity.
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Copy and paste a formatted citation
Spandidos Publications style
Hu K, Pan X, Chen F, Qin R, Wu L, Zhu H, Wu F, Ge J, Han W, Yin C, Yin C, et al: A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth. Int J Mol Med 33: 415-422, 2014.
APA
Hu, K., Pan, X., Chen, F., Qin, R., Wu, L., Zhu, H. ... Li, H. (2014). A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth. International Journal of Molecular Medicine, 33, 415-422. https://doi.org/10.3892/ijmm.2013.1574
MLA
Hu, K., Pan, X., Chen, F., Qin, R., Wu, L., Zhu, H., Wu, F., Ge, J., Han, W., Yin, C., Li, H."A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth". International Journal of Molecular Medicine 33.2 (2014): 415-422.
Chicago
Hu, K., Pan, X., Chen, F., Qin, R., Wu, L., Zhu, H., Wu, F., Ge, J., Han, W., Yin, C., Li, H."A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth". International Journal of Molecular Medicine 33, no. 2 (2014): 415-422. https://doi.org/10.3892/ijmm.2013.1574
Copy and paste a formatted citation
x
Spandidos Publications style
Hu K, Pan X, Chen F, Qin R, Wu L, Zhu H, Wu F, Ge J, Han W, Yin C, Yin C, et al: A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth. Int J Mol Med 33: 415-422, 2014.
APA
Hu, K., Pan, X., Chen, F., Qin, R., Wu, L., Zhu, H. ... Li, H. (2014). A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth. International Journal of Molecular Medicine, 33, 415-422. https://doi.org/10.3892/ijmm.2013.1574
MLA
Hu, K., Pan, X., Chen, F., Qin, R., Wu, L., Zhu, H., Wu, F., Ge, J., Han, W., Yin, C., Li, H."A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth". International Journal of Molecular Medicine 33.2 (2014): 415-422.
Chicago
Hu, K., Pan, X., Chen, F., Qin, R., Wu, L., Zhu, H., Wu, F., Ge, J., Han, W., Yin, C., Li, H."A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth". International Journal of Molecular Medicine 33, no. 2 (2014): 415-422. https://doi.org/10.3892/ijmm.2013.1574
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