ArticleChemico-biological interactions2012
The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance.
Article in Chemico-biological interactions, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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107 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.
- Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis.PloS one · 2015Pooled it
- Targeting ALDH7A1 with covalent inhibitors reveals new chemical space for prostate cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Development of retinoid nuclear receptor pathway antagonists through targeting aldehyde dehydrogenase 1A3.iScience · 2025Article
- Integrated Approach of Machine Learning and High-Throughput Screening to Identify Chemical Probe Candidates Targeting Aldehyde Dehydrogenases.ACS pharmacology & translational science · 2025Article
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- Article
- ALDEFLUOR activity, ALDH isoforms, and their clinical significance in cancers.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.Cancer letters · 2023Article
- Investigating Carvedilol's Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of β-Adrenergic Agonists.Current issues in molecular biology · 2023Article
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- Aldehyde Dehydrogenase, a Marker of Normal and Malignant Stem Cells, Typifies Mesenchymal Progenitors in Perivascular Niches.Stem cells translational medicine · 2023Article
- Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems.Pharmaceutics · 2023Review
- Characterization of Oogonial Stem Cells in Adult Mouse Ovaries with Age and Comparison to In Silico Data on Human Ovarian Aging.Stem cells and development · 2023Article
- The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression.Life (Basel, Switzerland) · 2023Review
- Identification and validation of a risk model and molecular subtypes based on tryptophan metabolism-related genes to predict the clinical prognosis and tumor immune microenvironment in lower-grade glioma.Frontiers in cellular neuroscience · 2023Article
- Zebrafish Model of Stickler Syndrome Suggests a Role for Col2a1a in the Neural Crest during Early Eye Development.Journal of developmental biology · 2022Article
- Mitochondrial Aldehyde Dehydrogenase 2 Represents a Potential Biomarker of Biochemical Recurrence in Prostate Cancer Patients.Molecules (Basel, Switzerland) · 2022Article
- Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency.Cancer gene therapy · 2022Review
- An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer.Molecular cancer · 2022Article
- Expansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Cancer.Journal of medicinal chemistry · 2022Article
47 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
There has been a new interest in using aldehyde dehydrogenase (ALDH) activity as one marker for stem cells since the Aldefluor flow cytometry-based assay has become available. Diethylaminobenzaldehyde (DEAB), used in the Aldeflour assay, has been considered a specific inhibitor for ALDH1A1 isoform. In this study, we explore the effects of human ALDH isoenzymes, ALDH1A2 and ALDH2, on drug resistance and proliferation, and the specificity of DEAB as an inhibitor. We also screened for the expression of 19 ALDH isoenzymes in K562 cells using TaqMan Low Density Array (TLDA). We used lentiviral vectors containing the full cDNA length of either ALDH2 or ALDH1A2 to over express the enzymes in K562 leukemia and H1299 lung cancer cell lines. Successful expression was measured by activity assay, Western blot, RT-PCR, and Aldefluor assay. Both cell lines, with either ALDH1A2 or ALDH2, exhibited higher cell proliferation rates, higher clonal efficiency, and increased drug resistance to 4-hydroperoxycyclophosphamide and doxorubicin. In order to study the specificity of known ALDH activity inhibitors, DEAB and disulfiram, we incubated each cell line with either inhibitor and measured the remaining ALDH enzymatic activity. Both inhibitors reduced ALDH activity of both isoenzymes by 65-90%. Furthermore, our TLDA results revealed that ALDH1, ALDH7, ALDH3 and ALDH8 are expressed in K562 cells. We conclude that DEAB is not a specific inhibitor for ALDH1A1 and that Aldefluor assay is not specific for ALDH1A1 activity. In addition, other ALDH isoenzymes seem to play a major role in the biology and drug resistance of various malignant cells.
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