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Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells
Ting Li1; Xiao-huang Xu1; Zheng-hai Tang1; Ya-fang Wang1; Chung-hang Leung1; Dik-lung Ma2; Xiu-ping Chen1; Yi-tao Wang1; Yi Chen3; Jin-jian Lu1,3
2015
Source PublicationActa Pharmacologica Sinica
ISSN1671-4083
Volume36Issue:12Pages:1503-1513
Abstract

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 μmol/L) inhibited the cell proliferation in vitro with IC50 values of 37.70±3.99, 24.30±2.30 and 19.70±2.36 μmol/L at 24, 48 and 72 h, respectively. Platycodin D (5-20 μmol/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 μmol/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 μmol/L) or BAF (50 nmol/L) significantly enhanced platycodin D-induced proliferation inhibition and apoptosis. Moreover, platycodin D (20 μmol/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.

KeywordApoptosis Autophagy Erk Baf Bel-7402 Cells Chloroquine Human Hepatocellular Carcinoma Jnk Platycodin d Sp600125 U0126
DOI10.1038/aps.2015.99
URLView the original
Indexed BySCI
Language英语
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:000366098300013
The Source to ArticleScopus
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Cited Times [WOS]:27   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong
3.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Ting Li,Xiao-huang Xu,Zheng-hai Tang,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 Ting Li.,Xiao-huang Xu.,Zheng-hai Tang.,Ya-fang Wang.,Chung-hang Leung.,...&Jin-jian Lu.(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 Ting Li,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.
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