Mariel E Toledo-Guzman , Miguel Ibanez-Hernandez, Angel A. Gomez-Gallegos and Elizabeth Ortiz-Sanchez* Pages 375 - 388 ( 14 )
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.
Aldehyde dehydrogenase, cancer stem cell, retinoic acid, all-trans-retinoic acid, stemness, isozyme.
Departamento de Bioquimica. Laboratorio de Terapia Genica. Escuela Nacional de Ciencias Biologicas. Posgrado de Biomedicina y Biotecnologia Molecular, Instituto Politecnico Nacional. Mexico City, Departamento de Bioquimica. Laboratorio de Terapia Genica. Escuela Nacional de Ciencias Biologicas. Posgrado de Biomedicina y Biotecnologia Molecular, Instituto Politecnico Nacional. Mexico City, Posgrado de Ciencias Biologicas. Universidad Nacional Autonoma de Mexico. Mexico City, Subdireccion de Investigacion Basica, Instituto Nacional de Cancerología. Av San Fernando 22. Colonia Seccion XVI. Tlalpan 14080. Mexico City