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

AMPK 抑制剂化合物 C 刺激神经酰胺产生并促进 MCF7 乳腺癌细胞中 Bax 重新分布和凋亡

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作者:Junfei Jin, Thomas D Mullen, Qi Hou, Jacek Bielawski, Alicja Bielawska, Xiaoming Zhang, Lina M Obeid, Yusuf A Hannun, Yi-Te Hsu

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.

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