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Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells

文献类型：期刊论文

作者Li, Ting2; Xu, Xiao-huang2; Tang, Zheng-hai2; Wang, Ya-fang2; Leung, Chung-hang2; Ma, Dik-lung1; Chen, Xiu-ping2; Wang, Yi-tao2; Chen, Yi3; Lu, Jin-jian2,3
刊名ACTA PHARMACOLOGICA SINICA
出版日期2015-12
卷号36期号:12页码:1503-1513
关键词platycodin D human hepatocellular carcinoma BEL-7402 cells apoptosis autophagy ERK JNK U0126 SP600125 chloroquine BAF
ISSN号1671-4083
DOI10.1038/aps.2015.99
文献子类Article
英文摘要Aim: Platycodin D, the main saponin isolated from Chinese herb Platycodonis Radix, exhibits anticancer activities against various cancer cell lines. Here we evaluated its anticancer action against human hepatocellular carcinoma cells in vitro and in vivo, and elucidated the relationship between platycodin D-induced apoptosis and autophagy. Methods: The viability of human hepatocellular carcinoma BEL-7402 cells was evaluated with MTT assay, and the apoptosis was examined using Annexin V/PI and Hoechst 33342 staining assays. Monodansylcadaverine (MDC) staining was used to label autophagic vacuoles. The proteins were detected using Western blot analysis. For studying its anticancer action in vivo, platycodin D (5 and 10 mg.kg(1).d(1)) was intraperitoneally injected to BEL-7402-bearing mice for 21 days. Results: Platycodin D (5-40 mu mol/L) inhibited the cell proliferation in vitro with IC50 values of 37.70 +/- 3.99, 24.30 +/- 2.30 and 19.70 +/- 2.36 mu mol/L at 24, 48 and 72 h, respectively. Platycodin D (5-20 mu mol/L) dose-dependently increased BEL-7402 cell apoptosis, increased the Bax/Bcl-2 ratio and the levels of cleaved PARP and cleaved caspase-3, and decreased the level of Bcl-2. Furthermore, platycodin D (5-20 mu mol/L) induced autophagy in BEL-7402 cells, as evidenced by formation of cytoplasmic vacuoles, increased amounts of LC3-II, and increased numbers of MDC-positive cells. Pretreatment with the autophagy inhibitor chloroquine (5 mu mol/L) or BAF (50 nmol/L) significantly enhanced platycodin D-induced proliferation inhibition and apoptosis. Moreover, platycodin D (20 mu mol/L) activated the ERK and JNK pathways in BEL-7402 cells, and simultaneous blockage of the two pathways effectively suppressed platycodin D-induced autophagy and enhanced platycodin D-induced apoptosis. In BEL-7402-bearing mice, platycodin D (10 mg.kg(1).d(1)) significantly reduced relative tumor volume with decreased body weight. Conclusion: Platycodin D not only inhibits the proliferation of BEL-7402 cells but also suppresses BEL-7402 xenograft tumor growth. Platycodin D-induced cell proliferation inhibition and apoptosis are amplified by co-treatment with autophagy inhibitors
WOS关键词CANCER CELLS ; TELOMERASE ACTIVITY ; PROTEIN-KINASES ; LEUKEMIA-CELLS ; HEPG2 CELLS ; GRANDIFLORUM ; INHIBITION ; ACTIVATION ; DEATH ; INDUCTION
资助项目Macao Science and Technology Development Fund[070/2013/A] ; University of Macau[MRG008-LJJ2014-ICMS] ; University of Macau[MYRG2015-00091-ICMS-QRCM] ; University of Macau[MYRG2015-00101-ICMS-QRCM] ; State Key Laboratory of Drug Research[SIMM1403KF-11]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5586899
WOS记录号WOS:000366098300013
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/276307]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Lu, Jin-jian
作者单位1.Hong Kong Baptist Univ, Dept Chem, Hong Kong, Peoples R China;
2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Li, Ting,Xu, Xiao-huang,Tang, Zheng-hai,et al. Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells[J]. ACTA PHARMACOLOGICA SINICA,2015,36(12):1503-1513.
APA Li, Ting.,Xu, Xiao-huang.,Tang, Zheng-hai.,Wang, Ya-fang.,Leung, Chung-hang.,...&Lu, Jin-jian.(2015).Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells.ACTA PHARMACOLOGICA SINICA,36(12),1503-1513.
MLA Li, Ting,et al."Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells".ACTA PHARMACOLOGICA SINICA 36.12(2015):1503-1513.

入库方式： OAI收割

来源：上海药物研究所

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