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 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.
Jin
Junfei
J
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Mullen
Thomas D
TD
Hou
Qi
Q
Bielawski
Jacek
J
Bielawska
Alicja
A
Zhang
Xiaoming
X
Obeid
Lina M
LM
Hannun
Yusuf A
YA
Hsu
Yi-Te
YT
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*
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