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      Sustained ERK activation-mediated proliferation inhibition of farrerol on human gastric carcinoma cell line by G0/G1-phase cell-cycle arrest.

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          Abstract

          Current cancer treatment is partly limited by chemotherapy-induced vascular toxicity associated with damage to vascular endothelial cells. In this study, the cytotoxicity of farrerol against SGC7901 gastric cancer cells and human umbilical vein endothelial cells (HUVECs) in vitro was investigated along with the underlying mechanisms of its growth-inhibitory effect against SGC7901 cells. MTT assays showed that farrerol inhibited SGC7901 cell growth, but exerted no cytotoxicity against HUVECs. Flow cytometry showed that treatment of SGC7901 cells with farrerol (5, 40, or 160 μmol/l) for 24 h caused G0/G1 cell cycle arrest in a concentration-dependent manner. Western blotting indicated that exposure of SGC7901 cells to farrerol resulted in significant upregulation of p27KIP1 (p27), accompanied by sustained activation of ERK1/2 and p38 MAPK instead of JNK. Farrerol-stimulated p27 expression, p38 MAPK activation, and cell growth inhibition were attenuated by pretreatment with U0126, an MEK1/2 inhibitor. In conclusion, this study indicates the selective cytotoxicity of farrerol against SGC7901 cells, but not HUVECs. Furthermore, it provides the first evidence that farrerol could induce cancer cell growth inhibition by G0/G1-phase cell-cycle arrest mediated by sustained ERK activation. The findings show the potential of farrerol as a chemotherapeutic agent without vascular toxicity for use against gastric cancer.

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          Author and article information

          Journal
          Eur. J. Cancer Prev.
          European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
          Ovid Technologies (Wolters Kluwer Health)
          1473-5709
          0959-8278
          Nov 2016
          : 25
          : 6
          Affiliations
          [1 ] aSchool of Pharmaceutical Science bDepartment of Physiology and the Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan cDepartment of Pharmacy, Beijing Friendship Hospital of the Capital Medical University, Beijing, People's Republic of China.
          Article
          10.1097/CEJ.0000000000000212
          26656929
          ede39540-9256-4589-aaad-18438fe73eee
          History

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