Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.

The superfamily of human aldehyde dehydrogenases (hALDHs) consists of 19 isoenzymes which are critical for several physiological and biosynthetic processes and play a major role in the organism's detoxification via the NAD(P) dependent oxidation of numerous endogenous and exogenous aldehyde substrates to their corresponding carboxylic acids. Over the last decades, ALDHs have been the subject of several studies as it was revealed that their differential expression patterns in various cancer types are associated either with carcinogenesis or promotion of cell survival. Here, we attempt to provide a thorough review of hALDHs' diverse functions and 3D structures with particular emphasis on their role in cancer pathology and resistance to chemotherapy. We are especially interested in findings regarding the association of structural features and their changes with effects on enzymes' functionalities. Moreover, we provide an updated outline of the hALDHs inhibitors utilized in experimental or clinical settings for cancer therapy. Overall, this review aims to provide a better understanding of the impact of ALDHs in cancer pathology and therapy from a structural perspective.

[1]  V. E. Fadouloglou,et al.  Identification of a peptide ligand for human ALDH3A1 through peptide phage display: Prediction and characterization of protein interaction sites and inhibition of ALDH3A1 enzymatic activity , 2023, Frontiers in Molecular Biosciences.

[2]  H. Issa,et al.  In Vitro Evaluation of ALDH1A3-Affinic Compounds on Breast and Prostate Cancer Cell Lines as Single Treatments and in Combination with Doxorubicin , 2023, Current issues in molecular biology.

[3]  Lixing Zhang,et al.  Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets , 2023, MedComm.

[4]  Aglaia Pappa,et al.  The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression , 2023, Life.

[5]  L. Fu,et al.  The ALDH2, IGSF9, and PRDM16 Proteins as Predictive Biomarkers for Prognosis in Breast Cancer. , 2022, Clinical breast cancer.

[6]  L. Holm,et al.  DALI shines a light on remote homologs: One hundred discoveries , 2022, Protein science : a publication of the Protein Society.

[7]  Chundi Gao,et al.  Development of a Clinical Prognostic Model for Metabolism-Related Genes in Squamous Lung Cancer and Correlation Analysis of Immune Microenvironment , 2022, BioMed research international.

[8]  C. Kuo,et al.  Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1 , 2022, Nature Chemical Biology.

[9]  M. Kumar,et al.  3D‐QSAR and scaffold hopping based designing of benzo[d]ox‐azol‐2(3H)‐one and 2‐oxazolo[4,5‐b]pyridin‐2(3H)‐one derivatives as selective aldehyde dehydrogenase 1A1 inhibitors: Synthesis and biological evaluation , 2022, Archiv der Pharmazie.

[10]  Mu-Kuan Chen,et al.  The impact of ALDH7A1 variants in oral cancer development and prognosis , 2022, Aging.

[11]  C. Arienti,et al.  Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance , 2022, Frontiers in Medicine.

[12]  X. Piao,et al.  Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention , 2022, International journal of molecular sciences.

[13]  N. Maitland,et al.  Expansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Cancer , 2022, Journal of medicinal chemistry.

[14]  X. Zhan,et al.  Comprehensive Analysis of Alteration Landscape and Its Clinical Significance of Mitochondrial Energy Metabolism Pathway-Related Genes in Lung Cancers , 2021, Oxidative medicine and cellular longevity.

[15]  C. Camacho,et al.  A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells , 2021, Communications Biology.

[16]  Z. Shao,et al.  ALDH1A1 Activity in Tumor-Initiating Cells Remodels Myeloid-Derived Suppressor Cells to Promote Breast Cancer Progression , 2021, Cancer Research.

[17]  J. Farrés,et al.  Design, Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors , 2021, Molecules.

[18]  M. Matúšková,et al.  Aldehyde dehydrogenase 1A1 and 1A3 isoforms – mechanism of activation and regulation in cancer , 2021, Cellular signalling.

[19]  J. Haybaeck,et al.  Deregulated glutamate to pro-collagen conversion is associated with adverse outcome in lung cancer and may be targeted by renin-angiotensin-aldosterone system (RAS) inhibition. , 2021, Lung cancer.

[20]  N. Chandel.  NADPH-The Forgotten Reducing Equivalent. , 2021, Cold Spring Harbor perspectives in biology.

[21]  V. E. Fadouloglou,et al.  Post-Translational Modifications: Host Defence Mechanism, Pathogenic Weapon, and Emerged Target of Anti-Infective Drugs , 2021, Frontiers in Anti-Infective Drug Discovery: Volume 9.

[22]  A. Djeghader,et al.  Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective , 2021, Frontiers in Molecular Biosciences.

[23]  D. Hong,et al.  Reply to Krupenko et al., Comment on “Lee et al. The Combination of Loss of ALDH1L1 Function and Phenformin Treatment Decreases Tumor Growth in KRAS-Driven Lung Cancer Cancers 2020, 12, 1382” , 2021, Cancers.

[24]  P. Bork,et al.  Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation , 2021, Nucleic Acids Res..

[25]  H. Jang,et al.  Overall survival of pancreatic ductal adenocarcinoma is doubled by Aldh7a1 deletion in the KPC mouse , 2021, Theranostics.

[26]  E. Aronica,et al.  A Selective Competitive Inhibitor of Aldehyde Dehydrogenase 1A3 Hinders Cancer Cell Growth, Invasiveness and Stemness In Vitro , 2021, Cancers.

[27]  T. Missihoun,et al.  Recent Development on Plant Aldehyde Dehydrogenase Enzymes and Their Functions in Plant Development and Stress Signaling , 2020, Genes.

[28]  Ying Lin,et al.  Perinatal Depression of Exposed Maternal Women in the COVID-19 Pandemic in Wuhan, China , 2020, Frontiers in Psychiatry.

[29]  C. La Motta,et al.  Aldehyde Dehydrogenases and Prostate Cancer: Shedding Light on Isoform Distribution to Reveal Druggable Target , 2020, Biomedicines.

[30]  J. Tanner,et al.  Inhibition, crystal structures, and in-solution oligomeric structure of aldehyde dehydrogenase 9A1. , 2020, Archives of biochemistry and biophysics.

[31]  M. Kokkinidis,et al.  Catalytic activity regulation through post-translational modification: the expanding universe of protein diversity , 2020, Advances in Protein Chemistry and Structural Biology.

[32]  Soo-Youl Kim,et al.  The Combination of Loss of ALDH1L1 Function and Phenformin Treatment Decreases Tumor Growth in KRAS-Driven Lung Cancer , 2020, Cancers.

[33]  John N. Hutchinson,et al.  Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers. , 2020, Blood.

[34]  C. La Motta,et al.  Imidazo[1,2-a]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells. , 2020, Journal of medicinal chemistry.

[35]  C. La Motta,et al.  Progress in the Field of Aldehyde Dehydrogenase Inhibitors: Novel Imidazo[1,2-a]pyridines against the 1A Family. , 2020, ACS medicinal chemistry letters.

[36]  F. Ursini,et al.  Lipid peroxidation and ferroptosis: The role of GSH and GPx4. , 2020, Free radical biology & medicine.

[37]  Wei Wu,et al.  Lipid Peroxidation Plays an Important Role in Chemotherapeutic Effects of Temozolomide and the Development of Therapy Resistance in Human Glioblastoma , 2020, Translational oncology.

[38]  Y. Osuga,et al.  Expression of ALDH1A Isozymes in Human Endometrium with and without Endometriosis and in Ovarian Endometrioma , 2020, Reproductive Sciences.

[39]  S. Donnini,et al.  ALDH3A1 Overexpression in Melanoma and Lung Tumors Drives Cancer Stem Cell Expansion, Impairing Immune Surveillance through Enhanced PD-L1 Output , 2019, Cancers.

[40]  N. Dokholyan,et al.  Development of a Novel Multi-Isoform ALDH Inhibitor Effective as an Antimelanoma Agent , 2019, Molecular Cancer Therapeutics.

[41]  H. Younus,et al.  Citral Inhibition of Human Salivary Aldehyde Dehydrogenase , 2019, Cell Biochemistry and Biophysics.

[42]  Y. Rojanasakul,et al.  The SOX9-Aldehyde Dehydrogenase Axis Determines Resistance to Chemotherapy in Non-Small-Cell Lung Cancer , 2019, Molecular and Cellular Biology.

[43]  N. Nordin,et al.  In Vivo Anti-Tumor Effects of Citral on 4T1 Breast Cancer Cells via Induction of Apoptosis and Downregulation of Aldehyde Dehydrogenase Activity , 2019, Molecules.

[44]  G. Moreno-Hagelsieb,et al.  Aldehyde dehydrogenase diversity in bacteria of the Pseudomonas genus. , 2019, Chemico-biological interactions.

[45]  L. Galluzzi,et al.  Metabolic enzymes expressed by cancer cells impact the immune infiltrate , 2019, Oncoimmunology.

[46]  E. Yoon,et al.  A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-like Cells. , 2019, Cell reports.

[47]  H. Rodemann,et al.  Nanog Signaling Mediates Radioresistance in ALDH-Positive Breast Cancer Cells , 2019, International journal of molecular sciences.

[48]  P. Bradshaw.  Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging , 2019, Nutrients.

[49]  K. Fink,et al.  A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma , 2019, Journal of Neuro-Oncology.

[50]  M. J. Masarudin,et al.  In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells , 2019, Scientific Reports.

[51]  R. Moreno-Sánchez,et al.  Role of Aldehyde Dehydrogenases in Physiopathological Processes. , 2019, Chemical research in toxicology.

[52]  Amaj Ahmed Laskar,et al.  Aldehyde toxicity and metabolism: the role of aldehyde dehydrogenases in detoxification, drug resistance and carcinogenesis , 2019, Drug metabolism reviews.

[53]  J. Tanner,et al.  Crystal Structure of Aldehyde Dehydrogenase 16 Reveals Trans-Hierarchical Structural Similarity and a New Dimer. , 2019, Journal of molecular biology.

[54]  D. Adams,et al.  ALDH1 Bio-activates Nifuroxazide to Eradicate ALDHHigh Melanoma-Initiating Cells , 2018, Cell chemical biology.

[55]  Wei Ma,et al.  Identification of cancer-type specific expression patterns for active aldehyde dehydrogenase (ALDH) isoforms in ALDEFLUOR assay , 2018, Cell Biology and Toxicology.

[56]  Geeta Mehta,et al.  Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy. , 2018, Journal of medicinal chemistry.

[57]  S. Okazaki,et al.  Synthetic lethality of the ALDH3A1 inhibitor dyclonine and xCT inhibitors in glutathione deficiency-resistant cancer cells , 2018, Oncotarget.

[58]  H. Eguchi,et al.  The mitochondrial one-carbon metabolic pathway is associated with patient survival in pancreatic cancer. , 2018, Oncology letters.

[59]  S. Ohdo,et al.  Optimized Dosing Schedule Based on Circadian Dynamics of Mouse Breast Cancer Stem Cells Improves the Antitumor Effects of Aldehyde Dehydrogenase Inhibitor. , 2018, Cancer research.

[60]  S. Darb-Esfahani,et al.  The prognostic impact of cancer stem-like cell biomarker aldehyde dehydrogenase-1 (ALDH1) in ovarian cancer: A meta-analysis. , 2018, Gynecologic oncology.

[61]  M. Matúšková,et al.  ALDH1A inhibition sensitizes colon cancer cells to chemotherapy , 2018, BMC Cancer.

[62]  Adam Yasgar,et al.  Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity , 2018, Journal of medicinal chemistry.

[63]  Chunfu Wu,et al.  Suppressing autophagy enhances disulfiram/copper‐induced apoptosis in non‐small cell lung cancer , 2018, European journal of pharmacology.

[64]  F. Feng,et al.  Clinicopathological characteristics and prognostic value of the cancer stem cell marker ALDH1 in ovarian cancer: a meta-analysis , 2018, OncoTargets and therapy.

[65]  J. Loscalzo,et al.  NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism. , 2018, Antioxidants & redox signaling.

[66]  C. Jeffery.  Protein moonlighting: what is it, and why is it important? , 2018, Philosophical Transactions of the Royal Society B: Biological Sciences.

[67]  H. Ishii,et al.  Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis , 2018, Scientific Reports.

[68]  Xiangchou Yang,et al.  Update of ALDH as a Potential Biomarker and Therapeutic Target for AML , 2018, BioMed research international.

[69]  P. Eyers,et al.  Live and let die: insights into pseudoenzyme mechanisms from structure. , 2017, Current opinion in structural biology.

[70]  J. P. Loria,et al.  Allostery in enzyme catalysis. , 2017, Current opinion in structural biology.

[71]  Jiri Bartek,et al.  Alcohol-abuse drug disulfiram targets cancer via p97 segregase adapter NPL4 , 2017, Nature.

[72]  Jong-Hee Chang,et al.  Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres , 2017, Neuro-oncology.

[73]  P. Mackenzie,et al.  Activation of ALDH1A1 in MDA-MB-468 breast cancer cells that over-express CYP2J2 protects against paclitaxel-dependent cell death mediated by reactive oxygen species. , 2017, Biochemical pharmacology.

[74]  Hongyu Zhao,et al.  Transcriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function. , 2017, Chemico-biological interactions.

[75]  M. Gasparetto,et al.  ALDHs in normal and malignant hematopoietic cells: Potential new avenues for treatment of AML and other blood cancers. , 2017, Chemico-biological interactions.

[76]  R. Franco,et al.  Human aldehyde dehydrogenase 3A1 (ALDH3A1) exhibits chaperone-like function. , 2017, The international journal of biochemistry & cell biology.

[77]  S. Tenbaum,et al.  ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment , 2017, Oncogene.

[78]  M. Salaspuro,et al.  ALDH2‐deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde , 2017, Regulatory toxicology and pharmacology : RTP.

[79]  Junwen Wang,et al.  NFATc2 enhances tumor-initiating phenotypes through the NFATc2/SOX2/ALDH axis in lung adenocarcinoma , 2017, bioRxiv.

[80]  Jeewon Kim,et al.  Targeting aldehyde dehydrogenase activity in head and neck squamous cell carcinoma with a novel small molecule inhibitor , 2017, Oncotarget.

[81]  E. Anderson,et al.  Biogenic Aldehydes as Therapeutic Targets for Cardiovascular Disease , 2017, Current opinion in pharmacology.

[82]  X. Wang,et al.  Decreased expression of ALDH5A1 predicts prognosis in patients with ovarian cancer , 2017, Cancer biology & therapy.

[83]  Che-Hong Chen,et al.  ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective , 2017, Journal of Biomedical Science.

[84]  Priyanka Chevour,et al.  Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition , 2017, Molecular carcinogenesis.

[85]  David W. Lee,et al.  Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells , 2017, Journal of experimental & clinical cancer research : CR.

[86]  C. La Motta,et al.  FOXD1-ALDH1A3 Signaling Is a Determinant for the Self-Renewal and Tumorigenicity of Mesenchymal Glioma Stem Cells. , 2016, Cancer research.

[87]  P. Marcato,et al.  Citral reduces breast tumor growth by inhibiting the cancer stem cell marker ALDH1A3 , 2016, Molecular oncology.

[88]  M. Duchen,et al.  Investigating mitochondrial redox state using NADH and NADPH autofluorescence , 2016, Free radical biology & medicine.

[89]  B. Mayer,et al.  Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin* , 2016, The Journal of Biological Chemistry.

[90]  Komaraiah Palle,et al.  Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets. , 2016, Annals of translational medicine.

[91]  C. Pirker,et al.  Anticancer metal drugs and immunogenic cell death. , 2016, Journal of inorganic biochemistry.

[92]  T. Yeh,et al.  ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients , 2016, Clinical Cancer Research.

[93]  Jihe Zhao.  Cancer stem cells and chemoresistance: The smartest survives the raid. , 2016, Pharmacology & therapeutics.

[94]  Kaori Tanaka,et al.  Aldehyde dehydrogenase 1A1 in stem cells and cancer , 2016, Oncotarget.

[95]  Yiming Yang,et al.  Aldehyde dehydrogenases and cancer stem cells. , 2015, Cancer letters.

[96]  Brian C. Jackson,et al.  Dead enzymes in the aldehyde dehydrogenase gene family: role in drug metabolism and toxicology , 2015, Expert opinion on drug metabolism & toxicology.

[97]  M. Baumann,et al.  Cancer stem cell related markers of radioresistance in head and neck squamous cell carcinoma , 2015, Oncotarget.

[98]  M. Ferrer,et al.  Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1). , 2015, Journal of medicinal chemistry.

[99]  Kaori Tanaka,et al.  ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma , 2015, Oncotarget.

[100]  G. Robertson,et al.  Disruption of Proline Synthesis in Melanoma Inhibits Protein Production Mediated by the GCN2 Pathway , 2015, Molecular Cancer Research.

[101]  C. Buchman,et al.  N,N-diethylaminobenzaldehyde (DEAB) as a substrate and mechanism-based inhibitor for human ALDH isoenzymes. , 2015, Chemico-biological interactions.

[102]  E. Morii,et al.  Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species. , 2015, Gynecologic oncology.

[103]  T. Peretz,et al.  A phase IIb trial assessing the addition of disulfiram to chemotherapy for the treatment of metastatic non-small cell lung cancer. , 2015, The oncologist.

[104]  M. Wirth,et al.  Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells. , 2015, Cancer research.

[105]  You-hong Cui,et al.  Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis. , 2015, American journal of cancer research.

[106]  T. Hurley,et al.  Characterization of two distinct structural classes of selective aldehyde dehydrogenase 1A1 inhibitors. , 2015, Journal of medicinal chemistry.

[107]  B. Liu,et al.  Notch3 functions as a regulator of cell self-renewal by interacting with the β-catenin pathway in hepatocellular carcinoma , 2015, Oncotarget.

[108]  J. Tanner,et al.  Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1. , 2015, ACS chemical biology.

[109]  Y. Xiong,et al.  NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells. , 2014, The Journal of clinical investigation.

[110]  J. Moreb,et al.  Aldehyde dehydrogenases in cancer: an opportunity for biomarker and drug development? , 2014, Drug discovery today.

[111]  In Gyu Kim,et al.  Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines. , 2014, Biochemical and biophysical research communications.

[112]  V. Thiviyanathan,et al.  Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas , 2014, International journal of oncology.

[113]  S. Sieber,et al.  Target discovery of acivicin in cancer cells elucidates its mechanism of growth inhibition , 2014, Chemical science.

[114]  F. Bertucci,et al.  Poly(ADP-Ribose) Polymerase 1 (PARP1) Overexpression in Human Breast Cancer Stem Cells and Resistance to Olaparib , 2014, PloS one.

[115]  R. LoPachin,et al.  Molecular Mechanisms of Aldehyde Toxicity: A Chemical Perspective , 2014, Chemical research in toxicology.

[116]  John D. Minna,et al.  Essential Role of Aldehyde Dehydrogenase 1A3 for the Maintenance of Non–Small Cell Lung Cancer Stem Cells Is Associated with the STAT3 Pathway , 2014, Clinical Cancer Research.

[117]  D. Matei,et al.  Beta-Catenin Regulated ALDH1A1 is a Target in Ovarian Cancer Spheroids , 2014, Oncogene.

[118]  Bo Wang,et al.  Enrichment of Chemical Libraries Docked to Protein Conformational Ensembles and Application to Aldehyde Dehydrogenase 2 , 2014, J. Chem. Inf. Model..

[119]  R. Schmid,et al.  Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDHhighCD44+ phenotype and sphere-forming capacity , 2014, BMC Cancer.

[120]  V. Vasiliou,et al.  Aldehyde dehydrogenases in acute myeloid leukemia , 2014, Annals of the New York Academy of Sciences.

[121]  M. Fishel,et al.  Development of Selective Inhibitors for Human Aldehyde Dehydrogenase 3A1 (ALDH3A1) for the Enhancement of Cyclophosphamide Cytotoxicity , 2014, Chembiochem : a European journal of chemical biology.

[122]  J. Ajani,et al.  ALDH‐1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients , 2014, Molecular oncology.

[123]  N. Magné,et al.  Targeting Head and Neck Cancer Stem Cells to Overcome Resistance to Photon and Carbon Ion Radiation , 2014, Stem Cell Reviews and Reports.

[124]  Daria Mochly-Rosen,et al.  Development of Selective Inhibitors for Aldehyde Dehydrogenases Based on Substituted Indole-2,3-diones , 2014, Journal of medicinal chemistry.

[125]  M. Fishel,et al.  Selective ALDH3A1 Inhibition by Benzimidazole Analogues Increase Mafosfamide Sensitivity in Cancer Cells , 2014, Journal of medicinal chemistry.

[126]  K. Ramana,et al.  4-Hydroxynonenal in the pathogenesis and progression of human diseases. , 2013, Current medicinal chemistry.

[127]  X. Xie,et al.  ALDH1 is an independent prognostic factor for patients with stages II–III rectal cancer after receiving radiochemotherapy , 2013, British Journal of Cancer.

[128]  M. Zabel,et al.  The role of aldehyde dehydrogenase (ALDH) in cancer drug resistance. , 2013, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[129]  J. Babich,et al.  The Role of Copper in Disulfiram-Induced Toxicity and Radiosensitization of Cancer Cells , 2013, The Journal of Nuclear Medicine.

[130]  Taro Saito,et al.  Distinct expression patterns and roles of aldehyde dehydrogenases in normal oral mucosa keratinocytes: differential inhibitory effects of a pharmacological inhibitor and RNAi-mediated knockdown on cellular phenotype and epithelial morphology , 2013, Histochemistry and Cell Biology.

[131]  P. Massion,et al.  ALDH7A1 expression is associated with recurrence in patients with surgically resected non-small-cell lung carcinoma. , 2013, Future oncology.

[132]  P. Benos,et al.  Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3 , 2013, Proceedings of the National Academy of Sciences.

[133]  Brian C. Jackson,et al.  Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. , 2013, Free radical biology & medicine.

[134]  Ying Chen,et al.  Aldehyde dehydrogenases: from eye crystallins to metabolic disease and cancer stem cells. , 2013, Chemico-biological interactions.

[135]  G. Fournet,et al.  α,β-Acetylenic amino thiolester inhibitors of aldehyde dehydrogenases 1&3: suppressors of apoptogenic aldehyde oxidation and activators of apoptosis. , 2013, Current medicinal chemistry.

[136]  M. Miyazaki,et al.  Aldehyde dehydrogenase 1 is associated with recurrence‐free survival but not stem cell‐like properties in hepatocellular carcinoma , 2012, Hepatology research : the official journal of the Japan Society of Hepatology.

[137]  M. McCarter,et al.  ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets , 2012, Stem cells.

[138]  G. Oberdorfer,et al.  Vascular Bioactivation of Nitroglycerin by Aldehyde Dehydrogenase-2 , 2012, The Journal of Biological Chemistry.

[139]  Vindhya Koppaka,et al.  Focus on molecules: ALDH1A1: from lens and corneal crystallin to stem cell marker. , 2012, Experimental eye research.

[140]  A. Pession,et al.  Retinoids in Pediatric Onco-Hematology: the Model of Acute Promyelocytic Leukemia and Neuroblastoma , 2012, Advances in Therapy.

[141]  Chin-Lee Wu,et al.  Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[142]  R. Berkowitz,et al.  Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures , 2012, BMC Cancer.

[143]  Vindhya Koppaka,et al.  Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application , 2012, Pharmacological Reviews.

[144]  R. Stanton.  Glucose‐6‐phosphate dehydrogenase, NADPH, and cell survival , 2012, IUBMB life.

[145]  Alysha K Croker,et al.  Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44+ human breast cancer cells , 2012, Breast Cancer Research and Treatment.

[146]  C. Brocker,et al.  Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development. , 2012, Experimental hematology.

[147]  Yu‐Chi Wang,et al.  Tumorigenesis and Neoplastic Progression ALDH 1-Bright Epithelial Ovarian Cancer Cells Are Associated with CD 44 Expression , Drug Resistance , and Poor Clinical Outcome , 2012 .

[148]  G. Muzio,et al.  Aldehyde dehydrogenases and cell proliferation. , 2012, Free radical biology & medicine.

[149]  Lung-Ji Chang,et al.  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. , 2012, Chemico-biological interactions.

[150]  H. Stefánsson,et al.  Identification of low-frequency variants associated with gout and serum uric acid levels , 2011, Nature Genetics.

[151]  Daria Mochly-Rosen,et al.  Discovery of a Novel Class of Covalent Inhibitor for Aldehyde Dehydrogenases* , 2011, The Journal of Biological Chemistry.

[152]  W. Keung,et al.  Differential Metabolism of Organic Nitrates by Aldehyde Dehydrogenase 1a1 and 2: Substrate Selectivity, Enzyme Inactivation, and Active Cysteine Sites , 2011, The AAPS Journal.

[153]  L. Tentori,et al.  Mutation Research/fundamental and Molecular Mechanisms of Mutagenesis Common Fragile Sites in Colon Cancer Cell Lines: Role of Mismatch Repair, Rad51 and Poly(adp-ribose) Polymerase-1 , 2022 .

[154]  M. Koch,et al.  Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer , 2011, BMC Cancer.

[155]  G. van der Pluijm,et al.  The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis , 2011, Clinical & Experimental Metastasis.

[156]  A. Allan,et al.  The Role of Human Aldehyde Dehydrogenase in Normal and Cancer Stem Cells , 2011, Stem Cell Reviews and Reports.

[157]  C. Brocker,et al.  Aldehyde dehydrogenase 7A1 (ALDH7A1) attenuates reactive aldehyde and oxidative stress induced cytotoxicity. , 2011, Chemico-biological interactions.

[158]  Siddikuzzaman,et al.  All Trans Retinoic Acid and Cancer , 2011, Immunopharmacology and immunotoxicology.

[159]  Brian C. Jackson,et al.  Update on the aldehyde dehydrogenase gene (ALDH) superfamily , 2011, Human Genomics.

[160]  Surendra Singh,et al.  Aldehyde dehydrogenase 1B1 (ALDH1B1) is a potential biomarker for human colon cancer. , 2011, Biochemical and biophysical research communications.

[161]  Laura A. Sullivan,et al.  Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. , 2010, Cancer research.

[162]  J. Yustein,et al.  High ALDH Activity Identifies Chemotherapy-Resistant Ewing's Sarcoma Stem Cells That Retain Sensitivity to EWS-FLI1 Inhibition , 2010, PloS one.

[163]  C. Eaves,et al.  Human Milk Protein Production in Xenografts of Genetically Engineered Bovine Mammary Epithelial Stem Cells , 2010, PloS one.

[164]  R. Bast,et al.  Targeting Aldehyde Dehydrogenase Cancer Stem Cells in Ovarian Cancer , 2010, Molecular Cancer Therapeutics.

[165]  Z. Rasheed,et al.  Isolation of Stem Cells from Human Pancreatic Cancer Xenografts , 2010, Journal of visualized experiments : JoVE.

[166]  Manuel Hidalgo,et al.  Tumor-initiating cells are rare in many human tumors. , 2010, Cell stem cell.

[167]  C. Brocker,et al.  Aldehyde Dehydrogenase 3B1 (ALDH3B1): Immunohistochemical Tissue Distribution and Cellular-specific Localization in Normal and Cancerous Human Tissues , 2010 .

[168]  M. Wicha,et al.  Single‐marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase , 2010, Head & neck.

[169]  R. Fiorelli,et al.  A novel classification of quiescent and transit amplifying adult neural stem cells by surface and metabolic markers permits a defined simultaneous isolation. , 2010, Stem cell research.

[170]  F. Hamdy,et al.  High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. , 2010, Cancer research.

[171]  Lin Zhang,et al.  Distinct Expression Levels and Patterns of Stem Cell Marker, Aldehyde Dehydrogenase Isoform 1 (ALDH1), in Human Epithelial Cancers , 2010, PloS one.

[172]  K. Kavanagh,et al.  Aldehyde Dehydrogenase 7A1 (ALDH7A1) Is a Novel Enzyme Involved in Cellular Defense against Hyperosmotic Stress* , 2010, The Journal of Biological Chemistry.

[173]  V. Laudet,et al.  From carrot to clinic: an overview of the retinoic acid signaling pathway , 2010, Cellular and Molecular Life Sciences.

[174]  J. Parry,et al.  The in vitro genotoxicity of ethanol and acetaldehyde. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[175]  Zhenqiu Liu,et al.  ALDH1A1 Is a Marker for Malignant Prostate Stem Cells and Predictor of Prostate Cancer Patients’ Outcome , 2009, Laboratory Investigation.

[176]  V. Vasiliou,et al.  The Aldehyde Dehydrogenase Gene Superfamily Resource Center , 2009, Human Genomics.

[177]  D. Overstreet,et al.  A selective ALDH-2 inhibitor reduces anxiety in rats , 2009, Pharmacology Biochemistry and Behavior.

[178]  D. Steindler,et al.  Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. , 2009, Cancer research.

[179]  D. Moscatelli,et al.  High Aldehyde Dehydrogenase Activity: A Novel Functional Marker of Murine Prostate Stem/Progenitor Cells , 2009, Stem cells.

[180]  Yi-Wei Chen,et al.  Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. , 2009, Biochemical and biophysical research communications.

[181]  Tao Zhang,et al.  Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. , 2009, Cancer research.

[182]  Feng Jiang,et al.  Aldehyde Dehydrogenase 1 Is a Tumor Stem Cell-Associated Marker in Lung Cancer , 2009, Molecular Cancer Research.

[183]  C. Blackstone,et al.  Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1 , 2009, neurogenetics.

[184]  H. Baker,et al.  ALDH isozymes downregulation affects cell growth, cell motility and gene expression in lung cancer cells , 2008, Molecular Cancer.

[185]  K. Chan,et al.  Aldehyde Dehydrogenase Discriminates the CD133 Liver Cancer Stem Cell Populations , 2008, Molecular Cancer Research.

[186]  C. Brocker,et al.  Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily , 2008, Expert opinion on drug metabolism & toxicology.

[187]  V. Vasiliou,et al.  The role of corneal crystallins in the cellular defense mechanisms against oxidative stress. , 2008, Seminars in cell & developmental biology.

[188]  Daniel Birnbaum,et al.  ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. , 2007, Cell stem cell.

[189]  Vasilis Vasiliou,et al.  Multiple and Additive Functions of ALDH3A1 and ALDH1A1 , 2007, Journal of Biological Chemistry.

[190]  V. Vasiliou,et al.  Mechanisms Involved in the Protection of UV-induced Protein Inactivation by the Corneal Crystallin ALDH3A1* , 2007, Journal of Biological Chemistry.

[191]  Q Ping Dou,et al.  Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. , 2006, Cancer research.

[192]  Vasilis Vasiliou,et al.  Scallop lens Ω-crystallin (ALDH1A9): A novel tetrameric aldehyde dehydrogenase , 2006 .

[193]  S. Shibutani,et al.  Increased DNA damage in ALDH2-deficient alcoholics. , 2006, Chemical research in toxicology.

[194]  J. Moreb,et al.  RNAi-mediated knockdown of aldehyde dehydrogenase class-1A1 and class-3A1 is specific and reveals that each contributes equally to the resistance against 4-hydroperoxycyclophosphamide , 2006, Cancer Chemotherapy and Pharmacology.

[195]  Y. Koutalos,et al.  Human Aldehyde Dehydrogenase 3A1 Inhibits Proliferation and Promotes Survival of Human Corneal Epithelial Cells* , 2005, Journal of Biological Chemistry.

[196]  Vasilis Vasiliou,et al.  Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family , 2005, Human Genomics.

[197]  T. Lister,et al.  Characterization of Cells with a High Aldehyde Dehydrogenase Activity from Cord Blood and Acute Myeloid Leukemia Samples , 2005, Stem cells.

[198]  D. Mohuczy,et al.  Retinoic Acid Down-Regulates Aldehyde Dehydrogenase and Increases Cytotoxicity of 4-Hydroperoxycyclophosphamide and Acetaldehyde , 2005, Journal of Pharmacology and Experimental Therapeutics.

[199]  A. Siraki,et al.  Aldehyde Sources, Metabolism, Molecular Toxicity Mechanisms, and Possible Effects on Human Health , 2005, Critical reviews in toxicology.

[200]  M. Picklo,et al.  Metabolism of 4-hydroxy-trans-2-nonenal by central nervous system mitochondria is dependent on age and NAD+ availability. , 2004, Chemical research in toxicology.

[201]  P. Chambon,et al.  A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[202]  Y. Koutalos,et al.  Aldh3a1 protects human corneal epithelial cells from ultraviolet- and 4-hydroxy-2-nonenal-induced oxidative damage. , 2003, Free radical biology & medicine.

[203]  R. V. van Montfort,et al.  Crystal structure of eta-crystallin: adaptation of a class 1 aldehyde dehydrogenase for a new role in the eye lens. , 2003, Biochemistry.

[204]  Timothy A J Haystead,et al.  Discovery of novel targets of quinoline drugs in the human purine binding proteome. , 2002, Molecular pharmacology.

[205]  U. Reichert,et al.  Novel competitive irreversible inhibitors of aldehyde dehydrogenase (ALDH1): restoration of chemosensitivity of L1210 cells overexpressing ALDH1 and induction of apoptosis in BAF(3) cells overexpressing bcl(2). , 2002, Biochemical pharmacology.

[206]  J. Stamler,et al.  Identification of the enzymatic mechanism of nitroglycerin bioactivation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[207]  J. Piatigorsky.  Enigma of the Abundant Water-Soluble Cytoplasmic Proteins of the Cornea: The “Refracton” Hypothesis , 2001, Cornea.

[208]  R. Grafström,et al.  Micro-array chip analysis of carbonyl-metabolising enzymes in normal, immortalised and malignant human oral keratinocytes , 2001, Cellular and Molecular Life Sciences CMLS.

[209]  F. Gabreëls,et al.  Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjögren-Larsson syndrome. , 2001, Brain : a journal of neurology.

[210]  M. Kirsch,et al.  NAD(P)H, a directly operating antioxidant? , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[211]  Z. Kozmík,et al.  Omega -crystallin of the scallop lens. A dimeric aldehyde dehydrogenase class 1/2 enzyme-crystallin. , 2000, The Journal of biological chemistry.

[212]  V. Vasiliou,et al.  Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. , 2000, Chemico-biological interactions.

[213]  E. Sausville,et al.  Identification of cytosolic aldehyde dehydrogenase 1 from non‐small cell lung carcinomas as a flavopiridol‐binding protein , 1999, FEBS letters.

[214]  P. Chambon,et al.  Embryonic retinoic acid synthesis is essential for early mouse post-implantation development , 1999, Nature Genetics.

[215]  K. Yamauchi,et al.  Xenopus Cytosolic Thyroid Hormone-binding Protein (xCTBP) Is Aldehyde Dehydrogenase Catalyzing the Formation of Retinoic Acid* , 1999, The Journal of Biological Chemistry.

[216]  T. Møller-Pedersen,et al.  The cellular basis of corneal transparency: evidence for 'corneal crystallins'. , 1999, Journal of cell science.

[217]  H. Baker,et al.  Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases. , 1998, Structure.

[218]  J. Piatigorsky,et al.  Multifunctional Lens Crystallins and Corneal Enzymes: More than Meets the Eye , 1998, Annals of the New York Academy of Sciences.

[219]  J. Lipsky,et al.  Inhibition of recombinant human mitochondrial and cytosolic aldehyde dehydrogenases by two candidates for the active metabolites of disulfiram. , 1997, Biochemistry.

[220]  C. G. Steinmetz,et al.  Structure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion. , 1997, Structure.

[221]  L. López-Fernández,et al.  The cytosolic aldehyde dehydrogenase gene (Aldh1) is developmentally expressed in Leydig cells , 1997, FEBS letters.

[222]  Yuh-Ju Sun,et al.  The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold , 1997, Nature Structural Biology.

[223]  H. Weiner,et al.  Binding of thyroxine analogs to human liver aldehyde dehydrogenases. , 1997, European journal of biochemistry.

[224]  E. Khairallah,et al.  Identification of a 54-kDa mitochondrial acetaminophen-binding protein as aldehyde dehydrogenase. , 1996, Toxicology and applied pharmacology.

[225]  D. Crabb,et al.  The mutation in the mitochondrial aldehyde dehydrogenase (ALDH2) gene responsible for alcohol-induced flushing increases turnover of the enzyme tetramers in a dominant fashion. , 1996, The Journal of clinical investigation.

[226]  D. Balasubramanian,et al.  Letter to the Editors: Corneal Aldehyde Dehydrogenase Displays Antioxidant Properties , 1996 .

[227]  A. Klyosov,et al.  Possible role of liver cytosolic and mitochondrial aldehyde dehydrogenases in acetaldehyde metabolism. , 1996, Biochemistry.

[228]  M. Gariboldi,et al.  The daunorubicin-binding protein of Mr 54,000 is an aldehyde dehydrogenase and is down-regulated in mouse liver tumors and in tumor cell lines. , 1994, Molecular pharmacology.

[229]  H. Nicholas,et al.  Aldehyde dehydrogenases: Widespread structural and functional diversity within a shared framework , 1993, Protein science : a publication of the Protein Society.

[230]  J. Piatigorsky,et al.  Aldehyde dehydrogenase-derived omega-crystallins of squid and octopus. Specialization for lens expression. , 1993, The Journal of biological chemistry.

[231]  F. J. G. M. Van Kuijk,et al.  Effects of ultraviolet light on the eye: role of protective glasses. , 1991 .

[232]  M. Kaufman,et al.  The 56 kDa androgen binding protein is an aldehyde dehydrogenase. , 1991, Biochemical and biophysical research communications.

[233]  L. Birnbaum,et al.  Metabolism of citral, an alpha,beta-unsaturated aldehyde, in male F344 rats. , 1990, Drug metabolism and disposition: the biological fate of chemicals.

[234]  E. Ortiz-Sánchez,et al.  ALDH as a Stem Cell marker in solid tumors. , 2018, Current stem cell research & therapy.

[235]  J. Shih,et al.  ALDH-positive lung cancer stem cells confer resistance to epidermal growth factor receptor tyrosine kinase inhibitors. , 2013, Cancer letters.

[236]  J Laterra,et al.  Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition , 2011, Oncogene.

[237]  T. Münzel,et al.  Nitrate reductase activity of mitochondrial aldehyde dehydrogenase (ALDH-2) as a redox sensor for cardiovascular oxidative stress. , 2010, Methods in molecular biology.

[238]  B. Levi,et al.  Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. , 2009, Blood.

[239]  V. Vasiliou,et al.  ALDH3A1: a corneal crystallin with diverse functions. , 2007, Experimental eye research.

[240]  N. Sládek.  Human aldehyde dehydrogenases: Potential pathological, pharmacological, and toxicological impact , 2003, Journal of biochemical and molecular toxicology.

[241]  P. Steinert,et al.  Sjögren–Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene , 1996, Nature Genetics.

[242]  T. Flynn,et al.  Enzymology and Molecular Biology of Carbonyl Metabolism 4 , 1993, Advances in Experimental Medicine and Biology.

[243]  H. Esterbauer,et al.  Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. , 1991, Free radical biology & medicine.

[244]  M. Kastan,et al.  Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells. , 1990, Blood.

[245]  H J Edenberg,et al.  Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. , 1989, The Journal of clinical investigation.

[246]  A Yoshida,et al.  Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. , 1984, Proceedings of the National Academy of Sciences of the United States of America.