Molecular mechanisms of Polyphyllin I-induced apoptosis and reversal of the epithelial-mesenchymal transition in human osteosarcoma cells

被引：53

作者：

Chang, Junli ^{[1
,2
]}

Wang, Hongshen ^{[1
,2
]}

Wang, Xianyang ^{[1
,2
]}

Zhao, Yongjian ^{[1
,2
]}

Zhao, Dongfeng ^{[1
,2
]}

Wang, Chenglong ^{[1
,2
]}

Li, Yimian ^{[1
,2
]}

Yang, Zhilie ^{[1
,2
]}

Lu, Sheng ^{[1
,2
]}

Zeng, Qinghua ^{[3
,4
]}

Zimmerman, Jacquelyn ^{[4
]}

Shi, Qi ^{[1
,2
]}

Wang, Yongjun ^{[1
,2
]}

Yang, Yanping ^{[1
,2
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Orthoped & Traumatol, Shanghai 200032, Peoples R China

[2] Shanghai Univ Tradit Chinese Med, Inst Spine, Shanghai 200032, Peoples R China

[3] Jilin Univ, Minist Educ, Key Lab Pathobiol, Changchun 130021, Peoples R China

[4] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2015年 / 170卷

基金：

中国博士后科学基金;

关键词：

Osteosarcoma; Proteasome activity; Polyphyllin I; Apoptosis; Cell cycle; Epithelialmesenchymal transition; NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PROTEASOME INHIBITORS; CANCER-CELLS; E-CADHERIN; GROWTH; BREAST; EPIDEMIOLOGY; METASTASIS;

D O I：

10.1016/j.jep.2015.05.006

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Osteosarcoma is a most common highly malignant bone tumor in children and adolescents. Polyphyllin I (PPI) is an ethanol extraction from Paris polyphylla Smith var.yunnanensis (Franch.) Hand.-Mazz, which belongs to antipyretic-detoxicate family and has been used as a natural medicine in the treatment of infectious disease and cancer in China for centuries. The proteasome activity inhibitory and anti-osteosarcoma effects of PPI have not been known. Here we found PPI exhibited a selective inhibitory effect on proteasomal chymotrypsin (CT)-like activity, both in purified human proteasome and in cultured osteosarcoma cellular proteasome, and caused an accumulation of ubiquitinated proteins. PPI also inhibited viability, proliferation, migration, and invasion of MG-63, Saos-2, and U-2 OS osteosarcoma cells and resulted in S phase arrest and apoptosis. Furthermore, we explored the molecular targets involved. Exposure of osteosarcoma cells to PPI caused an inactivation of the intrinsic nuclear factor kappa B (NF-kappa B) and activation of unfolded protein response (UPR)/endoplasmic reticulum (ER) stress signaling cascade in osteosarcoma cells, followed by down-regulation of anti-apoptotic proteins, with up-regulation of pro-apoptotic proteins. We also demonstrated down-regulation of c-Myc, Cyclin B1, Cyclin D1, and CDK1, which are involved in the cell cycle and growth. Finally, we identified down-regulation of Vimentin, Snail, Slug, and up-regulation of E-cadherin, which are integral proteins involved in epithelial mesenchymal transition (EMT). Taken together, our data provide insights into the mechanism underlying the anticancer activity of PPI in human osteosarcoma cells. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：117 / 127

页数：11

共 43 条

[1]

Adams J, 1999, CANCER RES, V59, P2615

[2] Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts [J].