Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells

Butyric acid and sphingomyelin (SM) affect colonic tumorigenesis. We examined the potential link between butyrate stimulation and SM metabolism in colonic and hepatic cancer cell lines. After incubating HT29 and HepG2 cells with butyrate and other short-chain fatty acids, we found that butyrate incr...

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Main Authors: Jun Wu, Yajun Cheng, Bo A.G. Jönsson, Åke Nilsson, Rui-Dong Duan
Format: Article
Language:English
Published: Elsevier 2005-09-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520329412
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author Jun Wu
Yajun Cheng
Bo A.G. Jönsson
Åke Nilsson
Rui-Dong Duan
author_facet Jun Wu
Yajun Cheng
Bo A.G. Jönsson
Åke Nilsson
Rui-Dong Duan
author_sort Jun Wu
collection DOAJ
description Butyric acid and sphingomyelin (SM) affect colonic tumorigenesis. We examined the potential link between butyrate stimulation and SM metabolism in colonic and hepatic cancer cell lines. After incubating HT29 and HepG2 cells with butyrate and other short-chain fatty acids, we found that butyrate increased acid but not neutral or alkaline sphingomyelinase (SMase) activity by 10- to 20-fold. The effects occurred after 16 h of incubation and were associated with reduced SM and phosphatidylcholine contents and increased ceramide levels. Northern blotting showed increased acid SMase mRNA levels in these cells after butyrate stimulation. Propionate was less potent, and acetate had no effect. No similar changes of acid phosphatase could be identified. At concentrations that increased acid SMase expression, butyrate inhibited cell proliferation, activated caspase 3, and induced apoptosis. However, the antiproliferative and apoptotic effects of butyrate preceded the changes of acid SMase and were not affected by knocking down acid SMase expression by small, interfering RNA. In addition, butyrate-induced acid SMase expression was not affected by blocking the caspase pathway.In conclusion, butyrate regulates SM metabolism by stimulating acid SMase expression in colon and liver cancer cells, but the increased acid SMase is not a critical mechanism for initiating the anticancer effects of butyrate.
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spelling doaj.art-2146a4371549464ba6786ae6ec7d248e2022-12-21T21:58:40ZengElsevierJournal of Lipid Research0022-22752005-09-0146919441952Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cellsJun Wu0Yajun Cheng1Bo A.G. Jönsson2Åke Nilsson3Rui-Dong Duan4Gastroenterology Laboratory, Biomedical Center B11, Lund University, S-221 84 Lund, SwedenGastroenterology Laboratory, Biomedical Center B11, Lund University, S-221 84 Lund, SwedenDepartment of Occupational and Environmental Medicine, Institute of Laboratory Medicine, University Hospital, S-221 85 Lund, SwedenGastroenterology Laboratory, Biomedical Center B11, Lund University, S-221 84 Lund, SwedenTo whom correspondence should be addressed.; Gastroenterology Laboratory, Biomedical Center B11, Lund University, S-221 84 Lund, SwedenButyric acid and sphingomyelin (SM) affect colonic tumorigenesis. We examined the potential link between butyrate stimulation and SM metabolism in colonic and hepatic cancer cell lines. After incubating HT29 and HepG2 cells with butyrate and other short-chain fatty acids, we found that butyrate increased acid but not neutral or alkaline sphingomyelinase (SMase) activity by 10- to 20-fold. The effects occurred after 16 h of incubation and were associated with reduced SM and phosphatidylcholine contents and increased ceramide levels. Northern blotting showed increased acid SMase mRNA levels in these cells after butyrate stimulation. Propionate was less potent, and acetate had no effect. No similar changes of acid phosphatase could be identified. At concentrations that increased acid SMase expression, butyrate inhibited cell proliferation, activated caspase 3, and induced apoptosis. However, the antiproliferative and apoptotic effects of butyrate preceded the changes of acid SMase and were not affected by knocking down acid SMase expression by small, interfering RNA. In addition, butyrate-induced acid SMase expression was not affected by blocking the caspase pathway.In conclusion, butyrate regulates SM metabolism by stimulating acid SMase expression in colon and liver cancer cells, but the increased acid SMase is not a critical mechanism for initiating the anticancer effects of butyrate.http://www.sciencedirect.com/science/article/pii/S0022227520329412short-chain fatty acidcolonliversphingomyelinapoptosiscaspase
spellingShingle Jun Wu
Yajun Cheng
Bo A.G. Jönsson
Åke Nilsson
Rui-Dong Duan
Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells
Journal of Lipid Research
short-chain fatty acid
colon
liver
sphingomyelin
apoptosis
caspase
title Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells
title_full Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells
title_fullStr Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells
title_full_unstemmed Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells
title_short Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in HT29 and HepG2 cells
title_sort acid sphingomyelinase is induced by butyrate but does not initiate the anticancer effect of butyrate in ht29 and hepg2 cells
topic short-chain fatty acid
colon
liver
sphingomyelin
apoptosis
caspase
url http://www.sciencedirect.com/science/article/pii/S0022227520329412
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