PMID- 22679478
OWN - NLM
STAT- MEDLINE
DCOM- 20120917
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Hydrogen sulfide lowers proliferation and induces protective autophagy in colon 
      epithelial cells.
PG  - e37572
LID - 10.1371/journal.pone.0037572 [doi]
LID - e37572
AB  - Hydrogen sulfide (H(2)S) is a gaseous bacterial metabolite that reaches high 
      levels in the large intestine. In the present study, the effect of H(2)S on the 
      proliferation of normal and cancerous colon epithelial cells was investigated. An 
      immortalized colon epithelial cell line (YAMC) and a panel of colon cancer cell 
      lines (HT-29, SW1116, HCT116) were exposed to H(2)S at concentrations similar to 
      those found in the human colon. H(2)S inhibited normal and cancerous colon 
      epithelial cell proliferation as measured by MTT assay. The anti-mitogenic effect 
      of H(2)S was accompanied by G(1)-phase cell cycle arrest and the induction of the 
      cyclin-dependent kinase inhibitor p21(Cip). Moreover, exposure to H(2)S led to 
      features characteristic of autophagy, including increased formation of LC3B(+) 
      autophagic vacuoles and acidic vesicular organelles as determined by 
      immunofluorescence and acridine orange staining, respectively. Abolition of 
      autophagy by RNA interference targeting Vps34 or Atg7 enhanced the 
      anti-proliferative effect of H(2)S. Further mechanistic investigation revealed 
      that H(2)S stimulated the phosphorylation of AMP-activated protein kinase (AMPK) 
      and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and S6 
      kinase. Inhibition of AMPK significantly reversed H(2)S-induced autophagy and 
      inhibition of cell proliferation. Collectively, we demonstrate that H(2)S 
      inhibits colon epithelial cell proliferation and induces protective autophagy via 
      the AMPK pathway.
FAU - Wu, Ya C
AU  - Wu YC
AD  - School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, 
      Hong Kong.
FAU - Wang, Xiao J
AU  - Wang XJ
FAU - Yu, Le
AU  - Yu L
FAU - Chan, Francis K L
AU  - Chan FK
FAU - Cheng, Alfred S L
AU  - Cheng AS
FAU - Yu, Jun
AU  - Yu J
FAU - Sung, Joseph J Y
AU  - Sung JJ
FAU - Wu, William K K
AU  - Wu WK
FAU - Cho, Chi H
AU  - Cho CH
LA  - eng
PT  - Journal Article
DEP - 20120529
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (MAP1LC3B protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.2.1.45 (ATG7 protein, human)
RN  - EC 6.2.1.45 (Autophagy-Related Protein 7)
RN  - EC 6.2.1.45 (Ubiquitin-Activating Enzymes)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 7
MH  - Cell Cycle/drug effects
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Class III Phosphatidylinositol 3-Kinases/metabolism
MH  - Colon/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Epithelial Cells/drug effects/*metabolism
MH  - Humans
MH  - Hydrogen Sulfide/*pharmacology
MH  - Intestinal Mucosa/drug effects/metabolism
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - Phagosomes/drug effects/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Ubiquitin-Activating Enzymes/metabolism
PMC - PMC3362591
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/09 06:00
MHDA- 2012/09/18 06:00
PMCR- 2012/05/29
CRDT- 2012/06/09 06:00
PHST- 2011/11/03 00:00 [received]
PHST- 2012/04/20 00:00 [accepted]
PHST- 2012/06/09 06:00 [entrez]
PHST- 2012/06/09 06:00 [pubmed]
PHST- 2012/09/18 06:00 [medline]
PHST- 2012/05/29 00:00 [pmc-release]
AID - PONE-D-11-21870 [pii]
AID - 10.1371/journal.pone.0037572 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e37572. doi: 10.1371/journal.pone.0037572. Epub 2012 May 29.