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

Autor: Junfei Jin, Thomas D. Mullen, Qi Hou, Jacek Bielawski, Alicja Bielawska, Xiaoming Zhang, Lina M. Obeid, Yusuf A. Hannun, Yi-Te Hsu
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Journal of Lipid Research, Vol 50, Iss 12, Pp 2389-2397 (2009)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.M900119-JLR200
Popis: 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.
Databáze: Directory of Open Access Journals