Dictyostelium discoideum to human cells: Pharmacogenetic studies demonstrate a role for sphingolipids in chemoresistance

被引:19
作者
Alexander, S [1 ]
Min, JX [1 ]
Alexander, H [1 ]
机构
[1] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2006年 / 1760卷 / 03期
关键词
cancer therapy; signal transduction modulator; MAP kinase; cisplatin; sphingosine; 1-phosphate; ceramide; glutathione;
D O I
10.1016/j.bbagen.2005.11.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Resistance to chemotherapy is a major obstacle for the treatment of cancer and a subject of extensive research. Numerous mechanisms of drug resistance have been proposed, and they differ for different drugs. Nevertheless, it is clear that our understanding of this important problem is still incomplete, and that new targets for modulating therapy still await discovery. The attractive biology and the availability of powerful molecular techniques have made the cellular slime mold Diclyostelium discoideum, a powerful non-mammalian model for drug target discovery, and the problem of drug resistance. To understand the molecular basis of chemoresistance to the widely used drug cisplatin, both genetic and pharmacological approaches have been applied to this versatile experimental system. These studies have resulted in the identification of novel molecular pathways which can be used to increase the efficacy of cisplatin, and brought attention to the role of sphingolipids in mediating the cellular response to chemotherapeutic drugs. In the following review, we will describe the history and utility of D. discoideum in pharmacogenetics, and discuss recent studies which focus attention on the role of sphingolipids in chemotherapy and chemoresistance. (C) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:301 / 309
页数:9
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