PMID- 22222116
OWN - NLM
STAT- MEDLINE
DCOM- 20120907
LR  - 20211203
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 12
IP  - 2
DP  - 2012 Feb
TI  - Involvement of melatonin in autophagy-mediated mouse hepatoma H22 cell survival.
PG  - 394-401
LID - 10.1016/j.intimp.2011.12.012 [doi]
AB  - The role of autophagy in cancer is controversial. Melatonin has been linked to 
      several aspects of cancer progression and also to regulation of autophagy. 
      Whether melatonin is involved in an autophagy-induced tumor suppressor mechanism 
      or a cyto-protective mechanism is unknown. Therefore, we investigated the effects 
      of melatonin on autophagy and its upstream regulator. We found that melatonin 
      triggers an autophagic process by enhancing Beclin 1 expression and inducing a 
      conversion of microtubule-associated protein 1 light chain 3(LC3)-I to LC3-II, 
      the protein associated with the autophagosome membrane, in hepatoma H22 
      tumor-bearing mice. Moreover, melatonin inhibits the phosphorylation of the 
      mammalian target of the rapamycin (mTOR) and Akt. Knockdown of Beclin 1 by either 
      RNA interference or co-treatment with the autophagy inhibitor, 
      3-methyladenine(3-MA), significantly enhanced the melatonin-induced apoptosis in 
      mouse hepatoma H22 cells. Our data provides the first evidence that melatonin 
      induces protective autophagy that prevents mouse hepatoma H22 cells from 
      undergoing apoptosis. A combination of melatonin with an autophagy inhibitor 
      might be a useful therapeutic strategy for hepatocellular carcinoma.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Medical Oncology, The Military General Hospital of Beijing PLA, 
      Beijing, China.
FAU - Jia, Zhiling
AU  - Jia Z
FAU - Zhang, Xia
AU  - Zhang X
FAU - Hou, Jincai
AU  - Hou J
FAU - Wang, Li
AU  - Wang L
FAU - Hao, Shuling
AU  - Hao S
FAU - Ruan, Xinjian
AU  - Ruan X
FAU - Yu, Zhonghe
AU  - Yu Z
FAU - Zheng, Yongqiu
AU  - Zheng Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120102
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 5142-23-4 (3-methyladenine)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - JAC85A2161 (Adenine)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects/genetics
MH  - Apoptosis Regulatory Proteins/antagonists & 
      inhibitors/biosynthesis/genetics/metabolism
MH  - Autophagy/*drug effects/genetics
MH  - Beclin-1
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/genetics
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Liver Neoplasms, Experimental/drug therapy/genetics/metabolism/*pathology
MH  - Melatonin/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microtubule-Associated Proteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
EDAT- 2012/01/10 06:00
MHDA- 2012/09/08 06:00
CRDT- 2012/01/07 06:00
PHST- 2011/07/15 00:00 [received]
PHST- 2011/11/18 00:00 [revised]
PHST- 2011/12/16 00:00 [accepted]
PHST- 2012/01/07 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/09/08 06:00 [medline]
AID - S1567-5769(11)00474-7 [pii]
AID - 10.1016/j.intimp.2011.12.012 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2012 Feb;12(2):394-401. doi: 10.1016/j.intimp.2011.12.012. 
      Epub 2012 Jan 2.