ABSTRACT
Aldehyde dehydrogenase (ALDH) is an enzyme that participates in important cellular mechanisms as aldehyde detoxification and retinoic acid synthesis; moreover, ALDH activity is involved in drug resistance, a characteristic of cancer stem cells (CSCs). Even though ALDH is found in stem cells, CSCs and progenitor cells, this enzyme has been successfully used to identify and isolate cell populations with CSC properties from several tumor origins. ALDH is allegedly involved in cell differentiation through its product, retinoic acid. However, direct or indirect ALDH inhibition, using specific inhibitors or retinoic acid, has shown a reduction in ALDH activity, along with the loss of stem cell traits, reduction of cell proliferation, invasion, and drug sensitization. For these reasons, ALDH and retinoic acid are promising therapeutic targets. This review summarizes the current evidence for ALDH as a CSCs marker in solid tumors, as well as current knowledge about the functional roles of ALDH in CSCs. We discuss the controversy of ALDH activity to maintain CSC stemness, or conversely, to promote cell differentiation. Finally, we review the advances in using ALDH inhibitors as anti-cancer drugs.
Subject(s)
Aldehyde Dehydrogenase/analysis , Neoplasms/diagnosis , Neoplastic Stem Cells/enzymology , Biomarkers, Tumor/analysis , Humans , Neoplasms/enzymologyABSTRACT
Purpose: To investigate the use Aldefluor® and N, N - Dimethylaminobenzaldehyde (DEAB) to design a protocol to sort keratinocyte stem cells from cultured keratinocytes from burned patients. Methods: Activated Aldefluor® aliquots were prepared and maintained at temperature between 2 to 8°C, or stored at -20°C. Next, the cells were collected following the standard protocol of sample preparation. Results: Best results were obtained with Aldefluor® 1.5µl and DEAB 15 µl for 1 x 106 cells, incubated at 37°C for 15 minutes. Flow cytometer range for keratinocyte stem cells separation was evaluated. There were 14.8% of stem cells separated in one sample of keratinocyte culture used to pattern the protocol. After being defined the ideal concentration, the same test pattern was performed in other keratinocyte samples. We observed a final mean of 10.8%. Conclusion: Aldefluor® has been shown as a favorable marking of epidermal keratinocyte stem cells for subsequent separation on a flow cytometer, with detection of 10.8% of epidermal keratinocyte stem cells, in this protocol.(AU)
Subject(s)
Humans , Keratinocytes , Adult Stem Cells , Aldehyde Dehydrogenase/analysis , Flow Cytometry/methods , Clinical ProtocolsABSTRACT
This is an electrophoretic study of ALDH isozymes in post-mortem tissue extracts. Three different electrophoretic variants of the isozyme ALDH3 were found in the 100 individuals examined. One liver sample showed lack of ALDH1 activity, but it remains unknown whether this is due to genetic mechanisms. The other two isozymes--ALDH2 and ALDH4--did not show any variations.
Subject(s)
Aldehyde Dehydrogenase/analysis , Isoenzymes/analysis , Liver/enzymology , Stomach/enzymology , Aldehyde Dehydrogenase/genetics , Costa Rica , Electrophoresis , Female , Humans , Isoenzymes/genetics , Male , PhenotypeABSTRACT
This is an electrophoretic study of ALDH isozymes in post-mortem tissue extracts. There differente electrophoretic variants of the isosyme ALDH3 were found in the 100 individuals examined. One liver sample showed lack of ALDH1 activity, but it remains unknown whether this is due to genetic mechanism. The other two isosymes - ALDH2 and ALDH4 - did not show any variations.