title: A novel retinoic acid analog, 4-amino-2-trifluoromethyl-phenyl retinate, inhibits gastric cancer cell growth.
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.
authors: Department of General Surgery, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Kong-Wang
authors: KW
authors: Hu
authors: Department of Gynaecology and Obstetrics, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Xiao-Hua
authors: XH
authors: Pan
authors: School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Fei-Hu
authors: FH
authors: Chen
authors: Department of Pathology, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Rong
authors: R
authors: Qin
authors: Department of Radiotherapy, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Li-Ming
authors: LM
authors: Wu
authors: Department of General Surgery, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Hua-Gang
authors: HG
authors: Zhu
authors: School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Fan-Rong
authors: FR
authors: Wu
authors: School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors: Jin-Fang
authors: JF
authors: Ge
authors: Department of General Surgery, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Wen-Xiu
authors: WX
authors: Han
authors: Department of General Surgery, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Chun-Lin
authors: CL
authors: Yin
authors: Department of General Surgery, The First Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Hong-Jun
authors: HJ
authors: Li
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D012176:Retinoids / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: C585745:4-amino-2-trifluoromethyl-phenyl retinate; D012176:Retinoids; D018808:Transcription Factor AP-1; D014212:Tretinoin