Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death

Cereser, Catherine; Boget, Sophie; Parvaz, Parviz; Revol, A

doi:10.1016/s0300-483x(01)00401-2

Cited by 124 publications

(59 citation statements)

References 32 publications

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“…In each preparation, three separate portions of chloroform (100 mL each) were added to extract all organic soluble products. 1 H and 13 C NMR and ESI MS of the chloroform extract showed only DSF (when directly compared to authentic sample of DSF from Aldrich), and no formation of M(deDTC) 2 complexes was observed.…”

Section: Methodsmentioning

confidence: 94%

Disulfiram Facilitates Intracellular Cu Uptake and Induces Apoptosis in Human Melanoma Cells

et al. 2004

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The alcohol-abuse deterrent disulfiram (DSF) is shown to have a highly selective toxicity against melanoma in culture, inducing a largely apoptotic response, with much lower toxicity against several other cell lines. Melanoma cell lines derived from different stages (radial, vertical, and metastatic phase) were all sensitive to DSF treatment in vitro; melanocytes were only slightly affected. A required role of extracellular Cu is demonstrated for DSF toxicity. Low concentrations of DSF alone decreased the number of viable cells, and the addition of CuCl2 significantly enhanced the DSF-induced cell death to less than 10% of control. Significantly, the intracellular Cu concentration of melanoma cells increased rapidly upon DSF treatment. Both the intracellular Cu uptake and the toxicity induced by DSF were blocked by co-incubation with bathocuproine disulfonic acid (BCPD, 100 μM), a non-membrane-permeable Cu chelator. Chemical studies demonstrated a complicated, extracellular redox reaction between Cu(II) and DSF, which forms the complex Cu(deDTC)2 in high yield, accompanied by oxidative decomposition of small amounts of disulfiram. The Cu complex has somewhat higher activity against melanoma and is suggested to be the active agent in DSF-induced toxicity. The redox conversion of DSF was unique to Cu(II) and not engendered by the other common biological metal ions Fe(II or III), Mn(III), and Zn(II). The implications of this work are significant both in the possible treatment of melanoma as well as in limiting the known side-effects of DSF, which we propose may be diminished by cotreatment to decrease adventitious Cu.

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Section: Methodsmentioning

confidence: 94%

Disulfiram Facilitates Intracellular Cu Uptake and Induces Apoptosis in Human Melanoma Cells

et al. 2004

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“…The absorbance was read at 532 nm and 600 nm. The concentration of malondyaldehyde-thiobarbituric acid (MDA-TBA) complex was determined from the standard curve (15,16) and expressed in mg of cellular protein (17). Each experiment was repeated three times.…”

Section: Cell Survivalmentioning

confidence: 99%

Cytotoxic and Genotoxic Effects of the Quercetin/Lanthanum Complex on Human Cervical Carcinoma Cells In Vitro

Durgo

Halec

Šola

et al. 2011

Archives of Industrial Hygiene and Toxicology

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Quercetin is the main fl avonoid in diet with a potential in the treatment of cancer, cardiovascular, and neurodegenerative diseases. Due to its specifi c planar chemical structure, quercetin readily forms chelates with metal ions. Complexes of bioactive compounds and metal ions such as lanthanum often show strong cytotoxic and antitumour properties. The aim of this study was to compare the genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells with compare it to the effects of free ligands, quercetin, and lanthanum alone. The quercetin/lanthanum complex showed considerable cytotoxicity in the concentration range of (100 to 1000) mmol mL -1 and exposure time of three hours. The complex also induced a dose-dependent pro-oxidative effects and the formation of single-strand and double-strand DNA breaks. Although we obtained promising results on the cell level, future experiments should answer whether the quercetin/lanthanum complex is cancer-specific and stable enough in physiological conditions to make a potential new antitumour drug. Arh Hig Rada Toksikol 2011;62:221-227 Evidence abounds about antitumour activity of small-molecule compounds, including metal complexes with fl avonoids, which directly interact with DNA (1). Recently, much attention has also been paid to how cancer cell growth and apoptosis are affected by rare earth metals and compounds such as lanthanum and cerium salts (2, 3). KEY WORDS: chelates, DNA damage, fl avonoid/metal complexes, oxidative damage Durgo K et al. QUERCETIN/LANTHANUM COMPLEX EFFECTS ON HUMAN CERVICAL CARCINOMA CELLSLanthanum salts can arrest the cell cycle in the G1/S phase in leukemic cell lines (2) and inhibit telomerase activity in the lymphoblastoid tumour cell line (3). Both induce apoptotic events. Contrary to this effect observed in tumour cells, no effect could be determined in normal bone marrow haematopoietic cells (2). Lanthanum complexed with bioactive compounds from plants has shown even stronger cytotoxic effect than when administered alone (4), suggesting that electron transfer and oxidative stress are responsible for the cytotoxic effect. Kostova et al. (5) found that lanthanum complexes with biscoumarins caused apoptotic cell death of several leukaemia and lymphoma cell lines, causing DNA fragmentation and morphological changes. The authors believe that this cytotoxic effect depends on the metal-ligand structure. Wang et al. (1) analysed a lanthanum-naringenin Schiff-base complex and found that the ligands were coordinated to the lanthanum ion through deprotonated hydroxyl groups. This complex bound directly to calf-thymus DNA, probably through intercalation, while the same concentrations caused a strong cytotoxic effect on human leukaemia and lung adenocarcinoma cells. Intercalation is the main cytotoxic mechanism of numerous antitumour agents such as cisplatin, but their use is limited by drug resistance. Determination and synthesis of new agents

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“…After cooling with tap water, the absorbance of the samples was read at 532 nm and then at 600 nm (value of nonspecifi c absorbance). The concentration of malondyaldehyde-thiobarbituric acid (MDA-TBA) complex was calculated from the standard curve (17,18). Concentration of cellular proteins was estimated using the Bradford method (19).…”

Section: Measurement Of Lipid Peroxidationmentioning

confidence: 99%

Genotoxic Effects of Green Tea Extract on Human Laryngeal Carcinoma Cells In Vitro

Durgo

Kostić

Gradiški

et al. 2011

Archives of Industrial Hygiene and Toxicology

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Green tea (Camellia sinensis) contains several bioactive compounds which protect the cell and prevent tumour development. Phytochemicals in green tea extract (mostly fl avonoids) scavenge free radicals, but also induce pro-oxidative reactions in the cell. In this study, we evaluated the potential cytotoxic and prooxidative effects of green tea extract and its two main fl avonoid constituents epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on human laryngeal carcinoma cell line (HEp2) and its crossresistant cell line CK2. The aim was to see if the extract and its two fl avonoids could increase the sensitivity of the cisplatin-resistant cell line CK2 in comparison to the parental cell line. The results show that EGCG and green tea extract increased the DNA damage in the CK2 cell line during short exposure. The cytotoxicity of EGCG and ECG increased with the time of incubation. Green tea extract induced lipid peroxidation in the CK2 cell line. The pro-oxidant effect of green tea was determined at concentrations higher than those found in traditionally prepared green tea infusions.

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Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death

Cited by 124 publications

References 32 publications

Disulfiram Facilitates Intracellular Cu Uptake and Induces Apoptosis in Human Melanoma Cells

Disulfiram Facilitates Intracellular Cu Uptake and Induces Apoptosis in Human Melanoma Cells

Cytotoxic and Genotoxic Effects of the Quercetin/Lanthanum Complex on Human Cervical Carcinoma Cells In Vitro

Genotoxic Effects of Green Tea Extract on Human Laryngeal Carcinoma Cells In Vitro

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