title: Sustained ERK activation-mediated proliferation inhibition of farrerol on human gastric carcinoma cell line by G0/G1-phase cell-cycle arrest.
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.
authors.affiliation: 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.
authors.forename: Enli
authors.initials: E
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Shasha
authors.initials: S
authors.lastname: Shi
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.forename: Taigang
authors.initials: T
authors.lastname: Liang
authors.forename: Bowei
authors.initials: B
authors.lastname: Wu
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D002867:Chromones; C015881:farrerol; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3