Title | Phloretin induces cell cycle arrest and apoptosis of human glioblastoma cells through the generation of reactive oxygen species |
Authors | Liu, Yuanyuan Fan, Chenghe Pu, Lv Wei, Cui Jin, Haiqiang Teng, Yuming Zhao, Mingming Yu, Albert Cheung Hoi Jiang, Feng Shu, Junlong Li, Fan Peng, Qing Kong, Jian Pan, Bing Zheng, Lemin Huang, Yining |
Affiliation | Peking Univ, Hosp 1, Dept Neurol, Beijing 100034, Peoples R China. Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Sch Basic Med Sci, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China. Peking Univ, Neurosci Res Inst, Key Lab Neurosci, Beijing 100083, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Beijing 100083, Peoples R China. Capital Med Univ, Beijing Chao Yang Hosp, Dept Hepatobiliary Surg, Beijing 100043, Peoples R China. Peking Univ, Hosp 1, Dept Neurol, Beijing 100034, Peoples R China. Zheng, LM (reprint author), Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China. Zheng, LM (reprint author), Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Sch Basic Med Sci, Beijing 100191, Peoples R China. Zheng, LM (reprint author), Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China. |
Keywords | Phloretin Cell cycle arrest Apoptosis Reactive oxygen species Glioblastoma PERFUSED-RAT-LIVER CANCER-CELLS OVARIAN-CANCER COLON-CANCER KINASE EXPRESSION INHIBITOR ASSOCIATION ACTIVATION INDUCTION |
Issue Date | 2016 |
Publisher | JOURNAL OF NEURO-ONCOLOGY |
Citation | JOURNAL OF NEURO-ONCOLOGY.2016,128,(2),217-223. |
Abstract | Phloretin, a flavonoid present in various plants, has been reported to exert anticarcinogenic effects. However, the mechanism of its chemo-preventive effect on human glioblastoma cells is not fully understood. This study aimed to investigate the molecular mechanism of phloretin and its associated chemo-preventive effect in human glioblastoma cells. The results indicate that phloretin inhibited cell proliferation by inducing cell cycle arrest at the G0-G1 phase and induced apoptosis of human glioblastoma cells. Phloretin-induced cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclinD and cyclinE. Moreover, the PI3K/AKT/mTOR signaling cascades were suppressed by phloretin in a dose-dependent manner. In addition, phloretin triggered the mitochondrial apoptosis pathway and generated reactive oxygen species (ROS). This was accompanied by the up-regulation of Bax, Bak and c-PARP and the down-regulation of Bcl-2. The antioxidant agents N-acetyl-l-cysteine and glutathione weakened the effect of phloretin on glioblastoma cells. In conclusion, these results demonstrate that phloretin exerts potent chemo-preventive activity in human glioblastoma cells through the generation of ROS. |
URI | http://hdl.handle.net/20.500.11897/434473 |
ISSN | 0167-594X |
DOI | 10.1007/s11060-016-2107-z |
Indexed | SCI(E) PubMed |
Appears in Collections: | 第一医院 |