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

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