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

  • Junfei Jin
  • , Thomas D. Mullen
  • , Qi Hou
  • , Jacek Bielawski
  • , Alicja Bielawska
  • , Xiaoming Zhang
  • , Lina M. Obeid
  • , Yusuf A. Hannun
  • , Yi Te Hsu
  • Medical University of South Carolina
  • University of South China
  • Chinese Academy of Medical Sciences
  • Department of Veterans Affairs

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

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.

Original languageEnglish
Pages (from-to)2389-2397
Number of pages9
JournalJournal of Lipid Research
Volume50
Issue number12
DOIs
StatePublished - Dec 1 2009

Keywords

  • AMP-activated protein kinase signaling pathway
  • Cell death
  • Sphingolipid

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