AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells

AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells

Compound C is commonly used as an inhibitor of AMP-activated protein kinase (AMPK), which serves as a key energy sensor in cells. In this study, we found that Compound C treatment of MCF7 cells led to Bax redistribution from the cytoplasm to mitochondria and cell death. However, this effect does not...

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Main Authors: Junfei Jin, Thomas D. Mullen, Qi Hou, Jacek Bielawski, Alicja Bielawska, Xiaoming Zhang, Lina M. Obeid, Yusuf A. Hannun, Yi-Te Hsu
Format: Article
Language:English
Published: Elsevier 2009-12-01
Series:Journal of Lipid Research
Subjects:
AMP-activated protein kinase signaling pathway
sphingolipid
cell death
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520306623
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spelling doaj-1196f9908bd143d1a874528e684a44312021-04-28T05:56:06ZengElsevierJournal of Lipid Research0022-22752009-12-01501223892397AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cellsJunfei Jin0Thomas D. Mullen1Qi Hou2Jacek Bielawski3Alicja Bielawska4Xiaoming Zhang5Lina M. Obeid6Yusuf A. Hannun7Yi-Te Hsu8Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425; Research Center of Life Science, University of South China, Hengyang, Hunan 421001, P.R. ChinaDepartment of Medicine, Medical University of South Carolina, Charleston, SC 29425Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425; Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P.R. ChinaDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425To whom correspondence should be addressed; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425Compound C is commonly used as an inhibitor of AMP-activated protein kinase (AMPK), which serves as a key energy sensor in cells. In this study, we found that Compound C treatment of MCF7 cells led to Bax redistribution from the cytoplasm to mitochondria and cell death. However, this effect does not involve AMPK. In addition, we found that treatment with this compound leads to an enhanced ceramide production. Analyses by quantitative PCR and ceramide synthase activity assay suggest that ceramide synthase 5 (LASS/CerS 5) is involved in Compound C-induced ceramide upregulation. Downregulation of LASS/CerS 5 was found to attenuate Compound C-mediated ceramide production, Bax redistribution, and cell death.http://www.sciencedirect.com/science/article/pii/S0022227520306623AMP-activated protein kinase signaling pathwaysphingolipidcell death
collection DOAJ
language English
format Article
sources DOAJ
author Junfei Jin
Thomas D. Mullen
Qi Hou
Jacek Bielawski
Alicja Bielawska
Xiaoming Zhang
Lina M. Obeid
Yusuf A. Hannun
Yi-Te Hsu
spellingShingle Junfei Jin
Thomas D. Mullen
Qi Hou
Jacek Bielawski
Alicja Bielawska
Xiaoming Zhang
Lina M. Obeid
Yusuf A. Hannun
Yi-Te Hsu
AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
Journal of Lipid Research
AMP-activated protein kinase signaling pathway
sphingolipid
cell death
author_facet Junfei Jin
Thomas D. Mullen
Qi Hou
Jacek Bielawski
Alicja Bielawska
Xiaoming Zhang
Lina M. Obeid
Yusuf A. Hannun
Yi-Te Hsu
author_sort Junfei Jin
title AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
title_short AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
title_full AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
title_fullStr AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
title_full_unstemmed AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells
title_sort ampk inhibitor compound c stimulates ceramide production and promotes bax redistribution and apoptosis in mcf7 breast carcinoma cells
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2009-12-01
description Compound C is commonly used as an inhibitor of AMP-activated protein kinase (AMPK), which serves as a key energy sensor in cells. In this study, we found that Compound C treatment of MCF7 cells led to Bax redistribution from the cytoplasm to mitochondria and cell death. However, this effect does not involve AMPK. In addition, we found that treatment with this compound leads to an enhanced ceramide production. Analyses by quantitative PCR and ceramide synthase activity assay suggest that ceramide synthase 5 (LASS/CerS 5) is involved in Compound C-induced ceramide upregulation. Downregulation of LASS/CerS 5 was found to attenuate Compound C-mediated ceramide production, Bax redistribution, and cell death.
topic AMP-activated protein kinase signaling pathway
sphingolipid
cell death
url http://www.sciencedirect.com/science/article/pii/S0022227520306623
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