Moreb Jan S
Department of Medicine, University of Florida, 1600 SW Archer Road, Po Box 100277, Gainesville, FL 32610, USA.
Curr Stem Cell Res Ther. 2008 Dec;3(4):237-46. doi: 10.2174/157488808786734006.
Multiple aldehyde dehydrogenase genes have been identified in many tissues. Aldehyde dehydrogenase class 1A1 (ALDH1A1) has been identified as highly expressed in embryonal tissue as well as in adult stem cells isolated from bone marrow, brain, breast and possibly other tissues. The recent interest in the idea of cancer stem cells (CSC) has resulted in renewed and vigorous interest in aldehyde dehydrogenase activity as a marker for those stem cells as well. It has been known that ALDH activity, which may reflect other ALDH isozymes in addition to ALDH1A1, is important for multiple biological activities including drug resistance, cell differentiation, and oxidative stress response. Purification of viable cells with high ALDH activity has become relatively easy with the availability of flow cytometry based assay. In this review, we examine the data available in regarding the importance of ALDH activity in normal and malignant stem cell functions, and the potential diagnostic and therapeutic implications. We review the available tools that can impact ALDH activity and may have the potential to be used therapeutically, specifically targeting the CSC. We raise questions that need to be investigated before a reasonable therapeutic strategy can be devised that will effectively inhibit ALDH activity.
在许多组织中已鉴定出多个醛脱氢酶基因。醛脱氢酶1A1类（ALDH1A1）已被确定在胚胎组织以及从骨髓、脑、乳腺和可能的其他组织中分离出的成体干细胞中高表达。最近对癌症干细胞（CSC）概念的关注导致对醛脱氢酶活性作为这些干细胞标志物的兴趣再次兴起且愈发强烈。已知醛脱氢酶活性除了反映ALDH1A1外，还可能反映其他ALDH同工酶，其对包括耐药性、细胞分化和氧化应激反应在内的多种生物学活性很重要。随着基于流式细胞术检测方法的出现，纯化具有高醛脱氢酶活性的活细胞变得相对容易。在本综述中，我们研究了有关醛脱氢酶活性在正常和恶性干细胞功能中的重要性以及潜在诊断和治疗意义的现有数据。我们回顾了可影响醛脱氢酶活性且可能具有治疗潜力的现有工具，特别是针对癌症干细胞的工具。我们提出了在设计出能有效抑制醛脱氢酶活性的合理治疗策略之前需要研究的问题。
