Aldehyde Dehydrogenases: Measurement of Activities and Protein Levels

Sreerama, Lakshmaiah; Sládek, Norman E.

doi:10.1002/0471140856.tx0418s26

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…B, proposed mechanism for ␤-elimination of Aldi-1, which yields two products, Aldi-1v and Aldi-1n. specifically, ALDH1A1 and ALDH3A1 activity was suggested as a predictor of efficacy against cyclophosphamide treatment in breast adenocarcinoma (34). Reduction of ALDH activity increases the sensitivity of the human lung adenocarcinoma cell line A549 to a metabolite of cyclophosphamide, 4-hydroxyperoxycyclophosphamide (5).…”

Section: Inhibition By Aldi Compounds Is Specific To Aldehydementioning

confidence: 99%

Discovery of a Novel Class of Covalent Inhibitor for Aldehyde Dehydrogenases

Khanna

Chen

Kimble-Hill

et al. 2011

Journal of Biological Chemistry

101

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Background: ALDH enzymes metabolize aldehydes in many pathways, including the inactivation of cyclophosphamide. Results: Covalent inhibitors against ALDH were discovered, and their mechanism of action was determined. Conclusion: Covalent inhibitors against ALDH potentiate cell killing in cyclophosphamide-resistant cells. Significance: These inhibitors represent novel research tools and can serve as leads toward therapeutics where increased ALDH activity is associated with disease.

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Section: Inhibition By Aldi Compounds Is Specific To Aldehydementioning

confidence: 99%

Discovery of a Novel Class of Covalent Inhibitor for Aldehyde Dehydrogenases

Khanna

Chen

Kimble-Hill

et al. 2011

Journal of Biological Chemistry

101

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“…It was originally designated as the tumor ALDH as it was found highly expressed in some human tumors such as hepatoma, lung adenocarcinoma, myeloma, breast cancer and stem cell populations. [20,21,22,23] It is also expressed in some normal human tissues such as cornea and keratinocytes. [18,24] Despite being present in normal cells, studies have shown that Aldh3a1(-/-) knockout mice are viable.…”

Section: Introductionmentioning

confidence: 99%

Development of Selective Inhibitors for Human Aldehyde Dehydrogenase 3A1 (ALDH3A1) for the Enhancement of Cyclophosphamide Cytotoxicity

et al. 2014

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Aldehyde dehydrogenase 3A1 (ALDH3A1) plays an important role in many cellular oxidative processes, including cancer chemo-resistance by metabolizing activated forms of oxazaphosphorine drugs such as cyclophosphamide (CP) and its analogues such as mafosfamide (MF), ifosfamide (IFM), 4-hydroperoxycyclophosphamide (4-HPCP). Compounds that can selectively target ALDH3A1 may permit delineation of its roles in these processes and could restore chemosensitivity in cancer cells that express this isoenzyme. Here we report the detailed kinetic and structural characterization of an ALDH3A1 selective inhibitor, CB29, previously identified in a high throughput screen. Kinetic and crystallographic studies demonstrate that CB29 binds within the aldehyde substrate-binding site of ALDH3A1. Cellular proliferation of ALDH3A1-expressing lung adenocarcinoma (A549) and glioblastoma (SF767) cell lines, as well as the ALDH3A1 non-expressing lung fibroblast cells, CCD-13Lu, is unaffected by treatment with CB29 and its analogues alone. However, the sensitivity toward the anti-proliferative effects of mafosfamide is enhanced by treatment with CB29 and its analogue in the tumour cells. In contrast, the sensitivity of CCD-13Lu cells toward mafosfamide was unaffected by the addition of these same compounds. CB29 is chemically distinct from the previously reported small molecule inhibitors of ALDH isoenzymes and does not inhibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1 or ALDH2 isoenzymes at concentrations up to 250 μM. Thus, CB29 is a novel small molecule inhibitor of ALDH3A1, which may be useful as a chemical tool to delineate the role of ALDH3A1 in numerous metabolic pathways, including sensitizing ALDH3A1-positive cancer cells to oxazaphosphorines.

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“…GSTM1 and GSTT1 have been shown to conjugate isothiocyanates, and in turn isothiocyanates have been shown to induce GSTs. Induction in enzyme activity occurs rapidly within several days of cruciferous vegetable consumption and declines with removal of the vegetables from the diet [72]. Polymorphisms in the GSTM1 and GSTT1 genes result in complete lack of GSTM1-1 and GSTT1-1 proteins, respectively.…”

Section: Discussionmentioning

confidence: 99%

Chemoprevention of Cancer by Isothiocyanates and Anthocyanins: Mechanisms of Action and Structure-Activity Relationship

Fimognari¹,

Lenzi²,

Hrelia

2008

CMC

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Carcinogenesis is a multi-step, multi-path and multi-focal process, which involves a series of epigenetic and genetic alterations that begin with genomic instability and end with the development of cancer. This long and complex process presents opportunities for the development of interventions both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Failure and high systemic toxicity of conventional cancer therapies have accelerated the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Now, it is recognized that diets rich in fruits and vegetables are associated with lower risk of cancer. Taking cue from these observations, there is a strong interest in isolating and characterizing the nutritive and non-nutritive components of fruits and vegetables as potential chemopreventive agents. Isothiocyanates and anthocyanins, present in widely consumed fruits and vegetables, are two such agents. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of isothiocyanates and anthocyanins in both in vitro and in vivo animal models. In this review article, we will provide detailed insight into the chemopreventive efficacy of isothiocyanates and anthocyanins based on the evidence generated from various studies performed using cell culture or animal models of epithelial cancers. Moreover, we will discuss the potential clinical relevance of the observed chemopreventive effects of these agents.

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Aldehyde Dehydrogenases: Measurement of Activities and Protein Levels

Cited by 5 publications

References 26 publications

Discovery of a Novel Class of Covalent Inhibitor for Aldehyde Dehydrogenases

Discovery of a Novel Class of Covalent Inhibitor for Aldehyde Dehydrogenases

Development of Selective Inhibitors for Human Aldehyde Dehydrogenase 3A1 (ALDH3A1) for the Enhancement of Cyclophosphamide Cytotoxicity

Chemoprevention of Cancer by Isothiocyanates and Anthocyanins: Mechanisms of Action and Structure-Activity Relationship

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