Aldehyde dehydrogenase inhibitors: α,β-Acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but irreversible apoptogens for cancer epithelial cells from human prostate in culture

Quash, G.; Fournet, Guy; Courvoisier, Charlotte; Martinez, Rosa M.; Chantepie, Jacqueline; Paret, Marie Julie; Pharaboz, Julie; Joly-Pharaboz, Marie Odile; Goré, J.; André, Jean

doi:10.1016/j.ejmech.2007.06.004

Cited by 19 publications

(15 citation statements)

References 17 publications

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“…The addition of DIMATE to BAF3bcl2 cells showed that cellular ALDH1 activity must be inhibited by at least 30% in order for 70% DNA fragmentation to take place [32]. An effect similar to that observed on BAF3bcl2 was also seen on the human prostate epithelial cancer cell line, DU145 [60]. On these cells DIMATE inhibited both ALDH1 & ALDH3, and induced the well-established [43] It is therefore apparent that the inhibition of ALDHs 1&3 induces apoptosis in cancer cells regardless of their species and tissue origin e.g.…”

Section: Ate Derivatives With Improved Apoptogenic-itysupporting

confidence: 54%

“…(dimethyl ampal thiolester, DI-MATE 2) and 4-morpholino-4-methyl-pent-2-ynthioic acid-Smethylester. (morpholino ampal thiolester, MATE 3) had a 70 to 90-fold improvement in growth-inhibitory activity (MATE IC 50 : 9 M; DIMATE IC 50 :7 M) compared to ATE IC 50 : (650 M) on DU145 [60]. The addition of DIMATE to BAF3bcl2 cells showed that cellular ALDH1 activity must be inhibited by at least 30% in order for 70% DNA fragmentation to take place [32].…”

Section: Ate Derivatives With Improved Apoptogenic-itymentioning

confidence: 96%

“…The growth of HPENC incubated with 10 M DIMATE for 3 days was retarded but resumed when the medium was removed and replaced by fresh medium without DIMATE [60] whereas no resumption of growth took place when their cancer counterparts DU145 cells were treated similarly in the same experiments [60].…”

Section: As a Reversible Cytostatic Agent On Human Prostate Epitheliamentioning

confidence: 99%

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α,β-Acetylenic Amino Thiolester Inhibitors of Aldehyde Dehydrogenases 1&3: Suppressors of Apoptogenic Aldehyde Oxidation and Activators of Apoptosis

Fournet¹,

Martin²,

Quash³

2013

Current Medicinal Chemistry

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The aim of this minireview is to recapitulate the evidence in the literature supporting a role for the aldehyde dehydrogenases (ALDH1, ALDH2 and ALDH3) in controlling the levels of 3 endogenous apoptogenic aldehydes: methional, malondialdehyde (MDA) and 4-hydroxynonenal (HNE). All 3 aldehydes are formed during the metabolism of cellular constituents. Methional is derived from the oxidative decarboxylation of 4-methylthio-2-oxobutanoate coming from the methionine salvage pathway. MDA arises from the peroxidation of lipids and also from methional subjected to attack by reactive oxygen species (ROS). HNE is formed primarily from lipid peroxidation by ROS attack. One major origin of ROS is the dysfunctional electron transport chain in the mitochondria of cancer cells. As bifunctional electrophilic compounds, HNE forms adducts with cellular nucleophiles e.g. GSH, whilst MDA acts as a potent DNA/protein cross-linking agent in vitro and in vivo. Cancer cells protect themselves from the apoptogenic effect of these aldehydes by the ALDHs that oxidize them to their non-apoptogenic carboxylic acids. Indeed, the over-expression of ALDH3 protects cells from HNE-induced apoptosis. The inhibition of ALDH1 allows methional to reach its apoptogenic threshold in BAF3bcl2 that were resistant to methionalinducible apoptosis. One member of the , -acetylenic N-substituted aminothiol ester family is an "active-enzyme-dependent", competitive, irreversible inhibitor of ALDH1 in vitro, an inhibitor of ALDH1 and ALDH3 in rat and human cancer cells in culture, an irreversible apoptogen on chemoresistant bcl2 +++ murine lymphoid and human epithelial cancer cells but a reversible cytostatic compound on human prostate epithelial normal cells in culture.

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Section: Ate Derivatives With Improved Apoptogenic-itysupporting

confidence: 54%

Section: Ate Derivatives With Improved Apoptogenic-itymentioning

confidence: 96%

Section: As a Reversible Cytostatic Agent On Human Prostate Epitheliamentioning

confidence: 99%

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α,β-Acetylenic Amino Thiolester Inhibitors of Aldehyde Dehydrogenases 1&3: Suppressors of Apoptogenic Aldehyde Oxidation and Activators of Apoptosis

Fournet¹,

Martin²,

Quash³

2013

Current Medicinal Chemistry

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“…These studies confirm the importance of the role of retinoid metabolism in the prostate. Various strategies are currently being pursued to identify useful agents for the treatment of prostate cancer, including ALDH inhibitors [65] and retinoic acid metabolism blocking agents [66].…”

Section: Discussionmentioning

confidence: 99%

High Aldehyde Dehydrogenase Activity: A Novel Functional Marker of Murine Prostate Stem/Progenitor Cells

et al. 2009

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We have shown previously that prostatic stem/progenitor cells can be purified from isolated prostate ducts, based on their high expression of the Sca-1 surface antigen. We now report that high levels of aldehyde dehydrogenase (ALDH) activity are present in a subset of prostate epithelial cells that coexpress a number of antigens found on stem/progenitor cells of other origins (CD9, Bcl-2, CD200, CD24, prominin, Oct 3/4, ABCG2, and nestin). Almost all of these cells expressing high levels of ALDH activity also express Sca-1 and a third of them express high levels of this antigen. The cells with high levels of ALDH activity have greater in vitro proliferative potential than cells with low ALDH activity. Importantly, in an in vivo prostate reconstitution assay, the cells expressing high levels of ALDH activity were much more effective in generating prostatic tissue than a population of cells with low enzymatic activity. Thus, a high level of ALDH activity can be considered a functional marker of prostate stem/progenitor cells and allows for simple, efficient isolation of cells with primitive features. The elucidation of the role of ALDH in prostate stem/progenitor cells may lead to the development of rational therapies for treating prostate cancer and benign prostatic hyperplasia. STEM CELLS

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“…In vitro ALDH1 inhibitory assay was performed as follows [9,10,16]. To a reaction mixture containing 1 mM EDTA, 100 mM KCl, 2 mM NAD, 0.1 M sodium phosphate buffer pH 7.4, 1 U/mg baker’s yeast ALDH1 was added by Multifunction microplatereader (Tecan Infinite 200, TECAN Austria GmbH, Männedorf, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Biological Evaluation and 3D-QSAR Studies of Curcumin Analogues as Aldehyde Dehydrogenase 1 Inhibitors

Wang

Zhang

et al. 2014

IJMS

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Aldehyde dehydrogenase 1 (ALDH1) is reported as a biomarker for identifying some cancer stem cells, and down-regulation or inhibition of the enzyme can be effective in anti-drug resistance and a potent therapeutic for some tumours. In this paper, the inhibitory activity, mechanism mode, molecular docking and 3D-QSAR (three-dimensional quantitative structure activity relationship) of curcumin analogues (CAs) against ALDH1 were studied. Results demonstrated that curcumin and CAs possessed potent inhibitory activity against ALDH1, and the CAs compound with ortho di-hydroxyl groups showed the most potent inhibitory activity. This study indicates that CAs may represent a new class of ALDH1 inhibitor.

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Aldehyde dehydrogenase inhibitors: α,β-Acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but irreversible apoptogens for cancer epithelial cells from human prostate in culture

Cited by 19 publications

References 17 publications

α,β-Acetylenic Amino Thiolester Inhibitors of Aldehyde Dehydrogenases 1&3: Suppressors of Apoptogenic Aldehyde Oxidation and Activators of Apoptosis

α,β-Acetylenic Amino Thiolester Inhibitors of Aldehyde Dehydrogenases 1&3: Suppressors of Apoptogenic Aldehyde Oxidation and Activators of Apoptosis

High Aldehyde Dehydrogenase Activity: A Novel Functional Marker of Murine Prostate Stem/Progenitor Cells

Biological Evaluation and 3D-QSAR Studies of Curcumin Analogues as Aldehyde Dehydrogenase 1 Inhibitors

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