title: Gambogic Acid lysinate induces apoptosis in breast cancer mcf-7 cells by increasing reactive oxygen species.
abstract: Gambogic acid (GA) inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited. Objectives. To investigate the antitumor activity of gambogic acid lysinate (GAL) and its mechanism. Methods. Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot. Results. GAL inhibited the proliferation of MCF-7 cells with IC50 values 1.46 μmol/L comparable with GA (IC50, 1.16 μmol/L). GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3. Conclusions. GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.
authors: Department of Histology and Embryology, Basic Medical College of Hebei United University, Tangshan 063000, China.
authors: Yong-Zhan
authors: YZ
authors: Zhen
authors: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing 100730, China.
authors: Ya-Jun
authors: YJ
authors: Lin
authors: Department of Histology and Embryology, Basic Medical College of Hebei United University, Tangshan 063000, China.
authors: Kai-Ji
authors: KJ
authors: Li
authors: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing 100730, China.
authors: Xiao-Shan
authors: XS
authors: Yang
authors: Department of Histology and Embryology, Basic Medical College of Hebei United University, Tangshan 063000, China.
authors: Yu-Fang
authors: YF
authors: Zhao
authors: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing 100730, China.
authors: Jie
authors: J
authors: Wei
authors: Department of Histology and Embryology, Basic Medical College of Hebei United University, Tangshan 063000, China.
authors: Jing-Bo
authors: JB
authors: Wei
authors: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing 100730, China.
authors: Gang
authors: G
authors: Hu