title: AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Junfei
authors.initials: J
authors.lastname: Jin
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Mullen
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
authors.forename: Jacek
authors.initials: J
authors.lastname: Bielawski
authors.forename: Alicja
authors.initials: A
authors.lastname: Bielawska
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.forename: Lina M
authors.initials: LM
authors.lastname: Obeid
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.forename: Yi-Te
authors.initials: YT
authors.lastname: Hsu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D021381:Protein Transport / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051049:Sphingosine N-Acyltransferase; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D002518:Ceramides; D011720:Pyrazoles; D011743:Pyrimidines; D051028:bcl-2-Associated X Protein; C516138:dorsomorphin; D010088:Oxidoreductases; C505722:CERS5 protein, human; D051049:Sphingosine N-Acyltransferase; D055372:AMP-Activated Protein Kinases