The Role of Aldehyde Dehydrogenase 1A1 in Stem Cells and Cancer Stem Cells

Abstract

Aldehyde dehydrogenase (ALDH) is a ubiquitous intracellular enzyme that catalyzes the irreversible oxidation of a variety of cellular aldehydes. High levels of ALDH activity, involving several isoforms of ALDH (ALDH1A1, ALDH1A2, ALDH1A3 and ALDH8A1), have been proposed as a common feature of stem cells. Adult hematopoietic, neural, and cancer stem cells have been reported to have high ALDH activity, decreased using Aldefluor, a fluorogenic substrate for ALDH. This activity has been attributed to ALDH1A1 expression, an enzyme that has been suggested to regulate stem cell function, including self-protection, differentiation, and expansion of stem cell populations. Recently, it was found that, in the liver, ALDH1A1 was expressed in almost all normal hepatocytes. However, ALDH1A1-overexpressing cells in hepatocellular carcinoma were not co-expressed with putative cancer stem cell markers CD133, CD13, CD90, BMI1, and EpCAM. In this respect, cancer stem cell target therapy related to ALDH1A1 should proceed with some caution; more detailed studies are needed because of this off-target toxicology. However, the subpopulation of cancer stem cells does represent a potential therapeutic target for poor-prognostic, treatment–resistant and recurrent cancer.