The cytotoxicity of dopamine may be an artefact of cell culture

Clément, Marie‐Véronique; Long, Lee Hua; Ramalingam, Jeyakumar; Halliwell, Barry

doi:10.1046/j.1471-4159.2002.00802.x

Cited by 124 publications

(76 citation statements)

References 36 publications

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“…The antilymphoma outcomes are, however, independent of both DAT and DA receptors, being delivered instead by extracellular oxidation. DA-induced toxicity through the generation of reactive oxidation species is well documented among cell line models of PD (26)(27)(28). In general, the concentrations of DA required for affecting neuronal cells via this route appear substantially higher than against the lymphoma lines used here.…”

Section: Discussionmentioning

confidence: 79%

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Meredith

Holder

Rosén

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Human B lymphocytes and derived lines from a spectrum of B cell malignancy were studied for expression of dopaminergic pathway components and for their cytostatic response to the catecholamine and related, potentially therapeutic compounds. Proliferating normal lymphocytes and dividing malignant clones rapidly arrested on exposure to dopamine in the low (<10 M) micromolar range. The antiparkinsonian drugs L-DOPA and apomorphine (particularly) were similarly antiproliferative. With the exception of D4, dopamine receptors D1-D5 were variably expressed among normal and neoplastic B cell populations, as was the dopamine transporter. Transcripts for D1 and D2 were frequently found, whereas D3 and D5 revealed restricted expression; dopamine transporter was detected in most cases. Nevertheless, pharmacological analysis disclosed that dopamine targeted cycling B cells independent of these structures. Rather, oxidative stress constituted the primary mechanism: the catecholamine's actions being mimicked by hydrogen peroxide and reversed by exogenous catalase, and evidence for the intracellular redox protein thioredoxin contributing protection. Among proliferating clones, growth arrest was accompanied by cell death in populations deplete in antiapoptotic Bcl-2: resting lymphocytes escaping low micromolar dopamine toxicity. Dysregulated bcl-2 expression, although preventing oxidative-induced caspase-dependent apoptosis, by itself conferred only minor protection against dopamine cytostasis. The selective impact of dopamine on lymphocytes that are in active cycle indicates an axis for therapeutic intervention not only in B cell neoplasia but also in lymphoproliferative disturbances generally. Rational tailoring of drug delivery systems already in development for Parkinson's disease could provide ideal vehicles for carrying the oxidative hit directly to the target populations.apoptosis ͉ oxidative stress ͉ Parkinson's disease ͉ Bcl-2 ͉ monoamines

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Section: Discussionmentioning

confidence: 79%

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Meredith

Holder

Rosén

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…[79,80] The stability of such compounds in the culture medium, and their propensity to produce ROS and other oxidation products, must be checked before beginning cell studies. Depending on the cell type and the amount of , quinones, and semiquinones generated by the oxidation of l-DOPA and dopamine in the culture medium [77] Toxicity of apple phenolics to cancer cells Due to oxidation to produce H 2 O 2 in the culture medium Cytotoxicity of gallic acid Largely or entirely due to oxidation of gallic acid to produce H 2 O 2 in the culture medium [72] Addition of grape seed extract to Caco-2 cell culture medium generates H 2 O 2 due to oxidation of phenolics in the medium [80] Toxicity of quercetin, catechin, and ascorbate to pancreatic β-cells Involves H 2 O 2 generation in the cell culture medium Toxicity of 4-methylcatechol to murine tumor cells Involves oxidation to form H 2 O 2 and quinones/semiquinones in the cell culture medium Toxicity of EGCG to ovarian cancer calls in DMEM Due to H 2 O 2 formation, probably both intracellularly and in the culture medium Stimulatory effects of garcinol on growth of intestinal cells Involves ROS production in the culture medium; [81] low levels of H 2 O 2 often stimulate cell proliferation [1,24] *Updated from Arch. Biochem.…”

Section: Resultsmentioning

confidence: 99%

“…3 May -June 2014 cytotoxic quinones/semiquinones that could be scavenged by adding GSH to the culture medium. [77] Sometimes they can lead to adaptations by activating the Nrf2 system. [67,78] …”

Section: 24]mentioning

confidence: 99%

Cell culture, oxidative stress, and antioxidants: Avoiding pitfalls

2014

Self Cite

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Cell culture is widely used by biochemists and cell/molecular biologists, but the fluctuating (and often elevated) levels of O 2 to which cells in culture are exposed can affect many of their properties. So can the low level of antioxidants found in some cell culture media. Reagents, especially "antioxidants," added to cell culture media can react with the constituents of the media to produce H 2 O 2 and degradation products that can influence cell behavior. Several published papers describing the cellular effects of ascorbate, polyphenols, and carotenoids have, in fact, reported artifacts due to the actions of the degradation products of these "antioxidants." A greater awareness of the potential artifacts in cell culture studies is needed among the free radical/antioxidant community. (Biomed J 2014;37:99-105)

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“…It now becomes plausible that inadvertent reactions between NO and constituents of the bathing medium are responsible. Interestingly, the cytotoxicity of dopamine has recently been attributed to artifactual oxidative reactions occurring in tissue-culture media [40], although the ingredients responsible were not identified. Alternatively, the consumption of NO by the medium may render NO non-toxic, depending on its fate therein.…”

Section: Discussionmentioning

confidence: 99%

Superoxide-dependent consumption of nitric oxide in biological media may confound in vitro experiments

Keynes

Griffiths

Garthwaite

2003

Biochemical Journal

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NO functions ubiquitously as a biological messenger but has also been implicated in various pathologies, a role supported by many reports that exogenous or endogenous NO can kill cells in tissue culture. In the course of experiments aimed at examining the toxicity of exogenous NO towards cultured cells, we found that most of the NO delivered using a NONOate (diazeniumdiolate) donor was removed by reaction with the tissue-culture medium. Two NO-consuming ingredients were identified : Hepes buffer and, under laboratory lighting, the vitamin riboflavin. In each case, the loss of NO was reversed by the addition of superoxide dismutase. The effect of Hepes was observed over a range of NONOate concentrations (producing up to 1 µM NO). Furthermore, from measurements of soluble guanylate cyclase activity, Hepes-dependent NO consumption remained significant at the low nanomolar NO concentrations relevant to physiological NO

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The cytotoxicity of dopamine may be an artefact of cell culture

Cited by 124 publications

References 36 publications

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Cell culture, oxidative stress, and antioxidants: Avoiding pitfalls

Superoxide-dependent consumption of nitric oxide in biological media may confound in vitro experiments

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