Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5827547 | European Journal of Pharmacology | 2015 | 8 Pages |
Abstract
Platycodin D (PD), isolated from the Chinese medicinal herb named Platycodonis Radix, is a triterpenoid saponin with well-known anti-tumor effects. In this study, we provided reliable evidence that PD triggered autophagy in a number of cell lines in vitro. PD-triggered autophagy was identified by observation of cytoplasmic vacuole, up-regulation of microtubule-associated protein 1 light chain 3 II (LC3-II), and accumulation of autophagosomes. The Akt/mammalian target of rapamycin (mTOR) pathway may be not involved in PD-triggered autophagy, as evidenced by the increased phosphorylation of Akt (Thr308), mTOR (Ser2448), ribosomal protein S6 kinase (Ser371), and ULK1 (Ser757). However, the extracellular signal-regulated kinase (ERK) was activated after PD treatment. The decreased ERK phosphorylation caused by pretreatment with U0126, an inhibitor of MEK, suppressed the expression of LC3-II compared with PD treatment alone, suggesting that ERK pathway may have a critical function in PD-triggered autophagy. In addition, the PD-induced proliferative inhibition and apoptosis were enhanced when pretreatment with autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (BAF), indicating that PD may trigger a protective autophagy in HepG2 cells. To the best of our knowledge, this paper is the first to report that PD triggers autophagy in a series of cell lines and ERK activation is important for PD-triggered autophagy in hepatocellular carcinoma HepG2 cells. The combined treatment with PD and CQ or BAF may be a promising regimen for hepatocellular carcinoma treatment.
Keywords
PARPPBSLC3FBSMDCHepG2p70S6KPVDFPMSFmTORBAFERKDMSOMTTAutophagybafilomycin A1ANOVADimethylsulfoxidefetal bovine serumphosphate buffer salinePhenylmethanesulfonyl fluorideProtectivemammalian target of rapamycinribosomal protein S6 kinasemicrotubule-associated protein 1 light chain 3Platycodin DPolyvinylidene fluoridepoly-ADP-ribose polymeraseChloroquineextracellular signal-regulated kinase
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Authors
Ting Li, Zheng-Hai Tang, Wen-Shan Xu, Guo-Sheng Wu, Ya-Fang Wang, Lin-Lin Chang, Hong Zhu, Xiu-Ping Chen, Yi-Tao Wang, Yi Chen, Jin-Jian Lu,