PMID- 25884331
OWN - NLM
STAT- MEDLINE
DCOM- 20160112
LR  - 20211203
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 16
IP  - 4
DP  - 2015 Apr 15
TI  - Autophagy induction by silibinin positively contributes to its anti-metastatic 
      capacity via AMPK/mTOR pathway in renal cell carcinoma.
PG  - 8415-29
LID - 10.3390/ijms16048415 [doi]
AB  - Silibinin, a dietary cancer chemopreventive flavonoid from the seeds of milk 
      thistle, has been reported to exhibit anti-metastatic effects on renal cell 
      carcinoma (RCC), but the mechanism underlying this phenomenon is not fully 
      understood. The present study aimed at examining the potential role of autophagy 
      in regulating silibinin-induced anti-metastatic effects on RCC cells. Using RCC 
      ACHN and 786-O cells as a model system in vitro, we found that silibinin 
      treatment increased the expression of LC3-II, resulted in the formation of 
      autophagolysosome vacuoles, and caused a punctate fluorescence pattern with the 
      monomeric red fluorescence protein-enhanced green fluorescence protein-LC3 
      (mRFP-EGFP-LC3) protein, which all are markers for cellular autophagy. Autophagy 
      flux was induced by silibinin in RCC cells, as determined by LC3 turnover assay. 
      Mechanically, the adenosine 5'-monophosphate activated protein kinase 
      (AMPK)/mammalian target of rapamycin (mTOR) pathway was identified as involved in 
      regulation of silibinin-induced autophagy. Furthermore, autophagy induction was 
      demonstrated to positively contribute to silibinin-induced anti-metastatic 
      effects on RCC cells in vitro. Activation of autophagy enhanced silibinin-induced 
      inhibition of migration and invasion of RCC cells, while inhibition of autophagy 
      attenuated it. These findings thus provide new information about the potential 
      link between autophagy and metastasis inhibition induced by silibinin, and the 
      induction of autophagy may shed some light into future treatment strategies for 
      metastatic RCC.
FAU - Li, Feng
AU  - Li F
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. tctx880315@gmail.com.
FAU - Ma, Zhenkun
AU  - Ma Z
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. mazhenkun.8@stu.xjtu.edu.cn.
FAU - Guan, Zhenfeng
AU  - Guan Z
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. guanzhenfeng@163.com.
FAU - Chen, Yule
AU  - Chen Y
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. xdwyd@stu.xjtu.edu.cn.
FAU - Wu, Kaijie
AU  - Wu K
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. yidaiwujin@126.com.
FAU - Guo, Peng
AU  - Guo P
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. guopeng661@mail.xjtu.edu.cn.
FAU - Wang, Xinyang
AU  - Wang X
AD  - Key Laboratory of Environment and Genes Related to Diseases, Ministry of 
      Education of China, Xi'an 710061, China. wangxinyang0929@163.com.
FAU - He, Dalin
AU  - He D
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. dalinhexjtu1@gmail.com.
AD  - Key Laboratory of Environment and Genes Related to Diseases, Ministry of 
      Education of China, Xi'an 710061, China. dalinhexjtu1@gmail.com.
FAU - Zeng, Jin
AU  - Zeng J
AD  - Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China. zengjin1984@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150415
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Silymarin)
RN  - 4RKY41TBTF (Silybin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.4.3 (Adenylate Kinase)
SB  - IM
MH  - Adenylate Kinase/metabolism
MH  - Antineoplastic Agents/*pharmacology
MH  - Autophagy/*drug effects
MH  - Carcinoma, Renal Cell/*drug therapy/secondary
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Signal Transduction
MH  - Silybin
MH  - Silymarin/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4425089
EDAT- 2015/04/18 06:00
MHDA- 2016/01/13 06:00
PMCR- 2015/04/15
CRDT- 2015/04/18 06:00
PHST- 2015/02/13 00:00 [received]
PHST- 2015/03/24 00:00 [revised]
PHST- 2015/04/03 00:00 [accepted]
PHST- 2015/04/18 06:00 [entrez]
PHST- 2015/04/18 06:00 [pubmed]
PHST- 2016/01/13 06:00 [medline]
PHST- 2015/04/15 00:00 [pmc-release]
AID - ijms16048415 [pii]
AID - ijms-16-08415 [pii]
AID - 10.3390/ijms16048415 [doi]
PST - epublish
SO  - Int J Mol Sci. 2015 Apr 15;16(4):8415-29. doi: 10.3390/ijms16048415.