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Metformin Induces G1 Cell Cycle Arrest and Inhibits Cell Proliferation in Nasopharyngeal Carcinoma Cells
Author(s) -
Zhao Li,
Wen ZhiHua,
Jia ChunHong,
Li Ming,
Luo ShenQiu,
Bai XiaoChun
Publication year - 2011
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21283
Subject(s) - ampk , mtorc1 , ribosomal protein s6 , biguanide , metformin , cell growth , cyclin b1 , cell cycle , cyclin d1 , nasopharyngeal carcinoma , dephosphorylation , protein kinase a , cancer research , microbiology and biotechnology , p70 s6 kinase 1 , amp activated protein kinase , biology , kinase , chemistry , phosphorylation , endocrinology , signal transduction , medicine , cell , cyclin dependent kinase 1 , pi3k/akt/mtor pathway , protein phosphorylation , biochemistry , phosphatase , radiation therapy , diabetes mellitus
It has been reported that metformin, a biguanide derivative widely used in type II diabetic patients, has antitumor activities in some cancers by activation of AMP‐activated protein kinase (AMPK). But its role in nasopharyngeal carcinoma (NPC) is not known. Here, we reported for the first time that 1–50 mM of metformin in a dose‐ and time‐dependent manner suppressed cell proliferation and colony formation in NPC cell line, C666‐1. Further studies revealed that the protein level of cyclin D1 decreased and the percentage of the cells in G0/G1 phase increased by 5 mM metformin treatment. Metformin also induced the phosphorylation of AMPK (T172) in a time‐dependent manner. Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)‐binding protein 1 (4E‐BP1) (T37/46) and S6 (S235/236) in C666‐1 cells. In a summary, metformin prevents proliferation of C666‐1 cells by down‐regulating cyclin D1 level and inducing G1 cell cycle arrest. AMPK‐mediated inhibition of mTORC1 signaling may be involved in this process. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.