Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells.
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3362591?pdf=render |
| _version_ | 1819100437630943232 |
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| author | Ya C Wu Xiao J Wang Le Yu Francis K L Chan Alfred S L Cheng Jun Yu Joseph J Y Sung William K K Wu Chi H Cho |
| author_facet | Ya C Wu Xiao J Wang Le Yu Francis K L Chan Alfred S L Cheng Jun Yu Joseph J Y Sung William K K Wu Chi H Cho |
| author_sort | Ya C Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T01:02:46Z |
| format | Article |
| id | doaj.art-04ddac0834be4a8a83cff3afb6bc7307 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:02:46Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-04ddac0834be4a8a83cff3afb6bc73072022-12-21T18:44:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3757210.1371/journal.pone.0037572Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells.Ya C WuXiao J WangLe YuFrancis K L ChanAlfred S L ChengJun YuJoseph J Y SungWilliam K K WuChi H ChoHydrogen 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.http://europepmc.org/articles/PMC3362591?pdf=render |
| spellingShingle | Ya C Wu Xiao J Wang Le Yu Francis K L Chan Alfred S L Cheng Jun Yu Joseph J Y Sung William K K Wu Chi H Cho Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. PLoS ONE |
| title | Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. |
| title_full | Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. |
| title_fullStr | Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. |
| title_full_unstemmed | Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. |
| title_short | Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. |
| title_sort | hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells |
| url | http://europepmc.org/articles/PMC3362591?pdf=render |
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