PMID- 29614812
OWN - NLM
STAT- MEDLINE
DCOM- 20180910
LR  - 20220408
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 4
DP  - 2018 Apr 2
TI  - 20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through 
      the Inhibition of PI3K/AKT/mTOR Signaling Pathway.
LID - 10.3390/ijms19041053 [doi]
LID - 1053
AB  - 20(S)-Protopanaxadiol (PPD) is one of the major active metabolites of ginseng. It 
      has been reported that 20(S)-PPD shows a broad spectrum of antitumor effects. Our 
      research study aims were to investigate whether apoptosis of human breast cancer 
      MCF-7 cells could be induced by 20(S)-PPD by targeting the Phosphatidylinositol 
      3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal 
      pathway in vitro and in vivo. Cell cycle analysis was performed by Propidium 
      Iodide (PI) staining. To overexpress and knock down the expression of mTOR, 
      pcDNA3.1-mTOR and mTOR small interfering RNA (siRNA) transient transfection 
      assays were used, respectively. Cell viability and apoptosis were evaluated by 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test and 
      Annexin V /PI double-staining after transfection. The antitumor effect in vivo 
      was determined by the nude mice xenograft assay. After 24 h of incubation, 
      treatment with 20(S)-PPD could upregulate phosphorylated-Phosphatase and tensin 
      homologue deleted on chromosome 10 (p-PTEN) expression and downregulate 
      PI3K/AKT/mTOR-pathway protein expression. Moreover, G0/G1 cell cycle arrest in 
      MCF-7 cells could be induced by 20(S)-PPD treatment at high concentrations. 
      Furthermore, overexpression or knockdown of mTOR could inhibit or promote the 
      apoptotic effects of 20(S)-PPD. In addition, tumor volumes were partially reduced 
      by 20(S)-PPD at 100 mg/kg in a MCF-7 xenograft model. Immunohistochemical 
      staining indicated a close relationship between the inhibition of tumor growth 
      and the PI3K/AKT/mTOR signal pathway. PI3K/AKT/mTOR pathway-mediated apoptosis 
      may be one of the potential mechanisms of 20(S)-PPD treatment.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun 130021, China. zlzhoan@163.com.
AD  - School of Materials Science and Engineering, South China University of 
      Technology, Guangzhou 510640, China. zlzhoan@163.com.
AD  - R&D Center, Guangzhou Ribobio Co., Ltd., Guangzhou 510663, China. 
      zlzhoan@163.com.
FAU - Xu, Hua-Li
AU  - Xu HL
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun 130021, China. xhl@jlu.edu.cn.
FAU - Wang, Yu-Chen
AU  - Wang YC
AUID- ORCID: 0000-0002-6064-9480
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun 130021, China. scarwyc@163.com.
FAU - Lu, Ze-Yuan
AU  - Lu ZY
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun 130021, China. zeyuanlu@jlu.edu.cn.
FAU - Yu, Xiao-Feng
AU  - Yu XF
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun 130021, China. xiaofengyu1962@163.com.
FAU - Sui, Da-Yun
AU  - Sui DY
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 
      Changchun 130021, China. suidy@jlu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20180402
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Sapogenins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - P6717R7BP8 (protopanaxadiol)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - MCF-7 Cells
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Sapogenins/*pharmacology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC5979555
OTO - NOTNLM
OT  - 20(S)-Protopanaxadiol
OT  - MCF-7
OT  - PI3K/AKT/mTOR
OT  - apoptosis
COIS- The authors declare no conflict of interest.
EDAT- 2018/04/05 06:00
MHDA- 2018/09/11 06:00
PMCR- 2018/04/01
CRDT- 2018/04/05 06:00
PHST- 2018/03/02 00:00 [received]
PHST- 2018/03/17 00:00 [revised]
PHST- 2018/03/27 00:00 [accepted]
PHST- 2018/04/05 06:00 [entrez]
PHST- 2018/04/05 06:00 [pubmed]
PHST- 2018/09/11 06:00 [medline]
PHST- 2018/04/01 00:00 [pmc-release]
AID - ijms19041053 [pii]
AID - ijms-19-01053 [pii]
AID - 10.3390/ijms19041053 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Apr 2;19(4):1053. doi: 10.3390/ijms19041053.