title: Platycodin D triggers autophagy through activation of extracellular signal-regulated kinase in hepatocellular carcinoma HepG2 cells.
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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Chang
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China; State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: jinjianlu@umac.mo.
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D018942:Macrolides; D012503:Saponins; D014315:Triterpenes; D002738:Chloroquine; C040929:bafilomycin A1; C108953:platycodin D; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Autophagy; Chloroquine; ERK; HepG2; Platycodin D; Protective