ONTD induces growth arrest and apoptosis of human hepatoma Bel-7402 cells though a peroxisome proliferator-activated receptor γ-dependent pathway.

Autor: Tan J; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China; Department of Pharmacology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China., Shen W; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China., Shi W; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China., Chen X; School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China., Sun D; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China., Xu C; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China., Yan Q; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China., Cheng H; The First Clinical Medical College, Nanjing University of Chinese Medicine, Key Laboratory of SATCM for Empirical Formulae Evaluation and Achievements Transformation, Collaborative Innovation Center of Jiangsu Province Chinese Medicine in Cancer Prevention and Treatment, Nanjing 210038, PR China. Electronic address: hbcheng@njucm.edu.cn., Lai Y; Department of Pharmacology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: lyscpu@cpu.edu.cn., Ji H; Department of Pharmacology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: jihuicpu@njucm.edu.cn.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2017 Dec; Vol. 45 (Pt 1), pp. 44-53. Date of Electronic Publication: 2017 Aug 20.
DOI: 10.1016/j.tiv.2017.08.012
Abstrakt: ONTD (3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile) is a novel synthetic derivative of glycyrrhetinic acid (GA), which has been reported to exhibit anti-inflammatory and anti-tumor activities through its mechanisms are not fully understood. Previously, we demonstrated that ONTD induces apoptosis of human hepatoma cells via a MAPK-dependent mitochondrial pathway. Recently, ONTD was found to increase sub-G1 accumulation and Annexin-V positive staining, indicating apoptotic induction effect. It was also be found that ONTD increase the PPAR-γ activity, reduce the phosphorylation of Akt and increase phosphatase and tensin homologue (PTEN) protein expression in hepatocellular carcinoma (HCC) Bel-7402 cells, and these were associated with the inhibition of cells proliferation. More importantly, these effects could be diminished by GW9662, a specific PPAR-γ antagonist, suggesting that ONTD can act as a ligand of PPAR-γ. Taken together, our novel observations suggested that ONTD may have potential implication in HCC prevention and treatment, and showed for the first time that the anti-tumor effect of ONTD may also be mediated through modulation of the PPAR-γ activation and mediated by the PTEN/Akt signaling pathway. The present study also supports ONTD as a potential drug candidate for chemoprevention or chemotherapy of HCC.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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