Polysaccharide from Phellinus linteus induces S-phase arrest in HepG2 cells by decreasing calreticulin expression and activating the P27kip1-cyclin A/D1/E-CDK2 pathway

文献类型: 外文期刊

第一作者: Li, You-Gui

作者: Li, You-Gui;Ji, Dong-Feng;Zhong, Shi;Liu, Pei-Gang;Lv, Zhi-Qiang;Zhu, Jian-Xun;Chen, Jin-E;Chen, Hua-Ping

作者机构:

关键词: Polysaccharide;S-phase arrest;Calreticulin;P27kip1;Cyclin/CDK complexes

期刊名称:JOURNAL OF ETHNOPHARMACOLOGY ( 影响因子:4.36; 五年影响因子:4.488 )

ISSN: 0378-8741

年卷期: 2013 年 150 卷 1 期

页码:

收录情况: SCI

摘要: Ethnopharmacology relevance: Our previous study showed that the proteoglycan P1 from Phellinus linteus (Mesima) exhibits significant anti-tumor activity against human hepatocellular carcinoma cells (HepG2); however, its molecular mechanism remains unknown. This study aims to provide insights into the mechanism of the anti-tumor activity of P1 against HepG2 cells. Methods: We examined the effects of P1 on HepG2 cell proliferation in vitro and in vivo. Flow cytometry was used to analyze the cell cycle distribution and apoptosis. Proteomic analysis, real-time (RT)-PCR, and Western blot were carried out to observe the expression of several cell cycle control proteins in HepG2 cells. Results: Both the volume and the weight of solid tumors were significantly decreased in P1-treated mice (200 mg/kg) compared with the control. The HepG2 cells in the P1-treated tumors were significantly decreased, irregularly shaped, and smaller. P1 slightly increased the body weight of the tumor-bearing mice, which indicates that P1 is nontoxic to mammals at 200 mg/kg. P1 also caused a significant dose-dependent increase in S phase arrest, but no apoptosis was observed in HepG2 cells. The results of the proteomic analysis, RT-PCR, and Western blot analysis showed that significantly downregulated expression of calreticulin, cyclin D1, cyclin E, and CDK2 and upregulated expression of P27kip1 and cyclin A in the P1-treated HepG2 cells (200 mu g/ml). Conclusion: These results suggest that calreticulin expression and the P27kip1-cydin A/D1/E-CDK2 pathway were involved in P1-induced S-phase cell cycle arrest in HepG2 cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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