PMID- 21608020
OWN - NLM
STAT- MEDLINE
DCOM- 20120412
LR  - 20171116
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 112
IP  - 10
DP  - 2011 Oct
TI  - Arctigenin enhances chemosensitivity of cancer cells to cisplatin through 
      inhibition of the STAT3 signaling pathway.
PG  - 2837-49
LID - 10.1002/jcb.23198 [doi]
AB  - Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, 
      Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has 
      been reported to exhibit anti-inflammatory activities, which is mainly mediated 
      through its inhibitory effect on nuclear transcription factor-kappaB (NF-kappaB). But 
      the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In 
      present study, we investigated the effect of arctigenin on signal transducer and 
      activator of transcription 3 (STAT3) pathway and evaluated whether suppression of 
      STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic 
      drug cisplatin. Our results show that arctigenin significantly suppressed both 
      constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent 
      nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine 
      phosphorylation was found to be achieved through suppression of Src, JAK1, and 
      JAK2, while suppression of STAT3 serine phosphorylation was mediated by 
      inhibition of ERK activation. Pervanadate reversed the arctigenin-induced 
      downregulation of STAT3 activation, suggesting the involvement of a protein 
      tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of 
      the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found 
      to be correlated to the resistance of cancer cells to cisplatin-induced 
      apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in 
      cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells 
      to cisplatin mainly via STAT3 suppression. These observations suggest a novel 
      anticancer function of arctigenin and a potential therapeutic strategy of using 
      arctigenin in combination with chemotherapeutic agents for cancer treatment.
CI  - Copyright (c) 2011 Wiley-Liss, Inc.
FAU - Yao, Xiangyang
AU  - Yao X
AD  - Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College 
      of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
FAU - Zhu, Fenfen
AU  - Zhu F
FAU - Zhao, Zhihui
AU  - Zhao Z
FAU - Liu, Chang
AU  - Liu C
FAU - Luo, Lan
AU  - Luo L
FAU - Yin, Zhimin
AU  - Yin Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Furans)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Lignans)
RN  - 0 (MYC protein, human)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (STAT3 Transcription Factor)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.3.2.27 (BIRC3 protein, human)
RN  - EC 2.3.2.27 (Baculoviral IAP Repeat-Containing 3 Protein)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U76MR9VS6M (arctigenin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Baculoviral IAP Repeat-Containing 3 Protein
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cisplatin/*pharmacology
MH  - Cyclin D1
MH  - Flow Cytometry
MH  - Furans/*pharmacology
MH  - G1 Phase/drug effects
MH  - HeLa Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/genetics/metabolism
MH  - Janus Kinase 1/genetics/metabolism
MH  - Janus Kinase 2/genetics/metabolism
MH  - Lignans/*pharmacology
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - Myeloid Cell Leukemia Sequence 1 Protein
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Proto-Oncogene Proteins c-myc/genetics/metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Ubiquitin-Protein Ligases
EDAT- 2011/05/25 06:00
MHDA- 2012/04/13 06:00
CRDT- 2011/05/25 06:00
PHST- 2011/05/25 06:00 [entrez]
PHST- 2011/05/25 06:00 [pubmed]
PHST- 2012/04/13 06:00 [medline]
AID - 10.1002/jcb.23198 [doi]
PST - ppublish
SO  - J Cell Biochem. 2011 Oct;112(10):2837-49. doi: 10.1002/jcb.23198.