Title | AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells |
Authors | Guan, Tong-ju Qin, Feng-jin Du, Jian-hai Geng, Li Zhang, You-yi Li, Min |
Affiliation | Lanzhou Univ, Sch Bas Med, Inst Pathol, Lanzhou 730000, Peoples R China. Peking Univ Hosp 3, Dept Obstet & Gynaecol, Beijing 100083, Peoples R China. Peking Univ Hosp 3, Inst Vascular Med, Key Lab Mol Cardiovasc Sci Minist Educ, Beijing 100083, Peoples R China. |
Keywords | AICAR proliferation apoptosis CaSki cells ACTIVATED PROTEIN-KINASE CERVICAL-CANCER CELLS THERAPEUTIC TARGET ERK ACTIVATION MTOR AMPK P53 CARCINOMA GROWTH CYCLE |
Issue Date | 2007 |
Publisher | 中国药理学报 |
Citation | ACTA PHARMACOLOGICA SINICA.2007,28,(12),1984-1990. |
Abstract | Aim: The aim of the present study was to determine the effect of 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR) on proliferation, cell cycle, and apoptosis in the human epithelial cervical cancer cell line CaSki cells. Methods: Cell count and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used to determine cell proliferation and viability. Hoechst 33258 staining was conducted to distinguish the apoptotic cells. Cell cycle and Annexin-V/propidium iodide staining were analyzed by fluorescence-activated cell sorting (FACS). A Western blot assay was used to evaluate the expression of AKT (also known as protein kinase B), mammalian target of rapamycin (mTOR), p53, and extracellular signal-regulated kinase (ERK). Results: AICAR (500 mu mol/L) significantly inhibited the proliferation of CaSki cells treated for 24, 48, and 72 h as determined by cell count. The cells at the G(1) and G(2) phases were dramatically decreased while cells at the S phase were increased in response to AICAR treatment for 24, 48, and 72 h. The MTT assay showed less viable cells and Hoechst fluorescent staining showed more apoptotic cells upon AICAR stimulation. The results of the Annexin-V staining demonstrated a time-dependent increase of apoptosis in cells treated with AICAR for 24, 36, and 48 h. Furthermore, AICAR activated caspase-3 in a time-dependent manner. It was also found that AICAR inhibited the phosphory-lation of AKT and mTOR, which are important kinases regulating cell growth and survival. AICAR stimulation obviously increased the expression of the tumor suppressor p53 and the phosphorylation of ERK. Conclusion: AICAR inhibited proliferation and induced S phase arrest and promoted apoptosis in CaSki cells, which might be mediated by the downregulation of the AKT/mTOR pathway and the upregulation of the p53/ERK pathway. |
URI | http://hdl.handle.net/20.500.11897/397976 |
ISSN | 1671-4083 |
DOI | 10.1111/j.1745-7254.2007.00675.x |
Indexed | SCI(E) 中国科技核心期刊(ISTIC) 中国科学引文数据库(CSCD) |
Appears in Collections: | 第三医院 |