PMID- 28534965
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20191210
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 38
IP  - 1
DP  - 2017 Jul
TI  - Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 
      signaling axis in human cisplatin resistant gastric cancer cells.
PG  - 271-278
LID - 10.3892/or.2017.5648 [doi]
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that 
      is overexpressed in multiple kinds of tumors including gastric cancer (GC). 
      Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in 
      GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell 
      growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' 
      in several cancer types to participate in the tumorigenic transformation and 
      chemoresistance. In the present study, we investigated whether 
      Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in 
      cisplatin (DDP)-resistant human GC cell line SGC7901/DDP. Results demonstrated 
      that CuB treatment significantly suppressed SGC7901/DDP cell proliferation, 
      induced caspase-dependent apoptosis, and autophagy. The activation of autophagy 
      was mediated through CuB-induced inhibition of mTORC1. Furthermore, CuB inhibited 
      mTORC1 via the activation of protein phosphatase 2A (PP2A) which is mediated by 
      CIP2A inhibition. These findings indicated that CuB can inhibit the 
      proliferation, induce caspase-dependent apoptosis, and autophagy of SGC7901/DDP 
      cells by suppressing CIP2A/PP2A/mTORC1 signaling axis. Thus, CuB may be a novel 
      effective candidate to treat DDP-resistant human GC cells.
FAU - Liu, Xuewen
AU  - Liu X
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Duan, Chao
AU  - Duan C
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Ji, Juanli
AU  - Ji J
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Zhang, Te
AU  - Zhang T
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Yuan, Xiaoning
AU  - Yuan X
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Zhang, Yunfei
AU  - Zhang Y
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Ma, Wenjing
AU  - Ma W
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
FAU - Yang, Jingyuan
AU  - Yang J
AD  - Hubei Province Key Laboratory of Conservation Biology for Shennongjia Golden 
      Monkey, Shennongjia National Nature Reserve, Shennongjia Forestry Region, 
      Shennongjia, Hubei 442400, P.R. China.
FAU - Yang, Linsen
AU  - Yang L
AD  - Hubei Province Key Laboratory of Conservation Biology for Shennongjia Golden 
      Monkey, Shennongjia National Nature Reserve, Shennongjia Forestry Region, 
      Shennongjia, Hubei 442400, P.R. China.
FAU - Jiang, Zhiguo
AU  - Jiang Z
AD  - Hubei Province Key Laboratory of Conservation Biology for Shennongjia Golden 
      Monkey, Shennongjia National Nature Reserve, Shennongjia Forestry Region, 
      Shennongjia, Hubei 442400, P.R. China.
FAU - Yu, Huiliang
AU  - Yu H
AD  - Hubei Province Key Laboratory of Conservation Biology for Shennongjia Golden 
      Monkey, Shennongjia National Nature Reserve, Shennongjia Forestry Region, 
      Shennongjia, Hubei 442400, P.R. China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical 
      Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170518
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Autoantigens)
RN  - 0 (CIP2A protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Triterpenes)
RN  - 0115W5MABF (cucurbitacin B)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Autoantigens/metabolism
MH  - Autophagy/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cisplatin/*pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Membrane Proteins/metabolism
MH  - Protein Phosphatase 2/metabolism
MH  - Signal Transduction
MH  - Stomach Neoplasms/drug therapy/metabolism/*pathology
MH  - Triterpenes/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2017/05/24 06:00
MHDA- 2018/05/16 06:00
CRDT- 2017/05/24 06:00
PHST- 2016/11/13 00:00 [received]
PHST- 2017/05/08 00:00 [accepted]
PHST- 2017/05/24 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2017/05/24 06:00 [entrez]
AID - 10.3892/or.2017.5648 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Jul;38(1):271-278. doi: 10.3892/or.2017.5648. Epub 2017 May 18.