Hepatocarcinogenesis and Ceramide/Cholesterol Metabolism

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 27th of 59 in Chemistry, Medicinal

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Hepatocarcinogenesis and Ceramide/Cholesterol Metabolism



Anti-Cancer Agents in Medicinal Chemistry, 12(4): 364-375.

Author(s): Albert Morales, Montserrat Mari, Carmen Garcia-Ruiz, Anna Colell and Jose C Fernandez-Checa.

Affiliation: Centro Esther Koplowitz, C/ Rossello 151, 08036-Barcelona, Spain.

Abstract

Sphingolipids (SLs) and cholesterol are critical structural components of membrane bilayers. Although recent evidence has revealed an emerging role of both lipids in signaling pathways, their contribution to cancer development and treatment has been largely overlooked. Sphingolipids comprise a family of bioactive lipids with divergent roles in numerous cellular processes. In particular, ceramide is the prototype of SLs and identified as a cell death effector whose levels increase in response to apoptotic stimuli such as ionizing radiation or chemotherapy. In the liver, ceramide/cholesterol accumulation contributes to a wide range of pathologies, including the transition from steatosis to steatohepatitis, which can further progress to cirrhosis and hepatocellular carcinoma (HCC). Moreover, different studies have shown that either pharmacologic ceramide accumulation or systemic intravenous administration of liposomal ceramide is an effective approach against HCC. In addition, mitochondrial cholesterol trafficking has emerged as a novel factor regulating cell death pathways and HCC tumor growth and chemoresistance. Due to the poor efficacy of current HCC treatments, understanding the role of ceramide/cholesterol in HCC may open up novel avenues for therapy. Here we describe recent evidence indicating that ceramide-generating agents and/or pharmacological targeting of sphingolipid/cholesterol metabolism, alone or in combination with other chemotherapeutic compounds, may be a promising strategy in HCC management.

Keywords:

Mitochondria, Ceramide, Cancer cell biology, Chemotherapy, sphingomyelinases, ceramide and gangliosides, pro-apoptotic ceramides, chemotherapeutic agents, pathologies, transmembrane protein, Cholesterol .



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Article Details

Volume: 12
Issue Number: 4
First Page: 364
Last Page: 375
Page Count: 12
DOI: 10.2174/187152012800228689
Price: $58
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