Study of anti-tumorigenic actions of essential fatty acids in a murine mammary gland adenocarcinoma by micro-XRF.

In the present work, a statistical experiment based on the microscopy X-ray fluorescence technique was developed to evaluate the effect of diets rich in ω-3 and ω-6 polyunsaturated fatty acids on tumour tissues. Relative variations on the local content of P, S, Ca, Fe, Cu and Zn were analysed in the experiment. Neoplastic tissues were obtained from mammary gland adenocarcinomas inoculated in mice belonging to three different dietary groups: normal, rich in ω-3 and in ω-6 polyunsaturated fatty acids. Slices of 30 microns thick sections of these samples were scanned in the air atmosphere in areas of 5 mm × 5 mm with a spatial resolution of 50 microns using synchrotron radiation. Principal component analysis was employed to analyse the correlation between the X-ray fluorescence signals of P, S, Ca, Fe, Cu and Zn. The subsequent application of the K-means clustering was used for the automatic segmentation of the image scans. By comparison with conventional histological analysis, the clusters were positively identified as tumour parenchyma, transition and necrotic region. The calculation of the mean content of P, S, Ca, Fe, Cu, and Zn in these regions showed that dietary polyunsaturated fatty acids modify elemental content of tumour parenchyma, suggesting its involvement in the antitumour effects of chia oil and protumour effects of safflower oil.

COVID-19-related stress in postpartum women from Argentina during the second wave in 2021: Identification of impairing and protective factors.

OBJECTIVE: Postpartum women are a vulnerable population to pandemic stressors that challenge their psychological well-being. Thus, reliable and valid instruments are necessary to measure pandemic-related stress and to identify risk and protective factors. This work aimed to assess psychometric properties of the COVID-19 Pandemic-Related Stress Scale (PSS-10-C) and associations of maternal pandemic stress with demographic, reproductive and pandemic factors of Argentinian postpartum women during the second COVID-19 wave. DESIGN: An online cross-sectional survey was conducted from April to June 2021. SETTING: Online recruitment of postpartum women was carried out during the second wave of COVID-19 in Argentina. This study was conducted in accordance with the Declaration of Helsinki and had the corresponding ethical approval. PARTICIPANTS: This study was performed on 300 women, aged 18-49 years, up to 12 months postpartum in Argentina. MEASUREMENTS AND FINDINGS: Stress was assessed with PSS-10-C, with a sociodemographic questionnaire being used to collect demographic, reproductive and pandemic variables. Statistical analysis included psychometric procedures, structural equation modeling, and multiple regressions. PSS-10-C was a reliable and structurally valid instrument with two subscales, with entire scale, Stress and Coping subscales scoring 17.31 (6.52), 9.70 (4.61) and 7.61 (2.77), respectively. History of mood disorders, pregnancy loss, and unhealthy child during the pandemic predisposed to increased stress (ß > 0.10, p < 0.05), whereas having work and practicing breastfeeding promoted coping to face it (ß < -0.13, p < 0.05). This situation was impaired by mood changes, loss of happiness, economic changes, fear of contracting COVID-19 -own or by a loved one- (ß > 0.11, p < 0.05). KEY CONCLUSIONS: The study highlighted the vulnerability of postpartum women's mental health in the pandemic context, with PSS-10-C being a useful instrument for clinicians and researchers to assess perceived stress. Targeting interventions toward women at higher risk can be highly beneficial for maternal and child health.

Memory enhancement in Argentinian women during postpartum by the dietary intake of lignans and anthocyanins.

Due to their polyphenolic content, vegetable foods have neuroprotective effects which provide health benefits for specific human groups. Thus, they may be a useful dietary component for women who experience mnesic variations during postpartum, and here we examined the hypothesis that polyphenols can differentially enhance memory functioning. In particular, we aimed to associate the dietary intake of polyphenols with different memory systems in Argentinian postpartum women. The daily intakes of polyphenol groups were calculated using a validated food frequency questionnaire and the Phenol-Explorer database. Short-term memory (STM), long-term memory (LTM), learning (L), lexical-semantic memory (LSM), and working memory (WM) were assessed. Partial Least Squares (PLS) regression models were used to analyze the dietary polyphenols (predictors) and memory domains (responses), taking into account demographic, obstetric, and psychological factors. The sample included 71 women, with an average age of 29.59 years (SE = 0.73). Most of these women lived in a couple (91%), were unemployed (63%), and had ≥12 years of formal education (72%). STM, LTM, L, and LSM correlated with lignans and anthocyanins, with LTM also being correlated with flavanones, flavonols, and tyrosols, and L and LSM also being associated with flavonols. A significant correlation was also found between WM and lignans. In conclusion, a cognitive improvement was demonstrated, mainly associated with the intake of lignans and anthocyanins, in the STM, LTM, WM, L, and LSM systems of postpartum women. This is the first study to our knowledge suggesting a role of polyphenolic effects on memory functioning during postpartum.

Age, education and gender effects on Wisconsin card sorting test: standardization, reliability and validity in healthy Argentinian adults.

The Wisconsin Card Sorting Test (WCST) is a widely used neuropsychological assessment of executive functioning. The aim of this study was to provide norm values and analyze the psychometric properties of WCST in healthy Argentinian adults aged from 18 to 89 years old (N = 235). Descriptive statistics are reported as means, standard deviations and percentiles, with the effects of age, education and gender being investigated by ANOVA, and with the effect sizes being calculated. The psychometrics were studied using the WCST structure, reliability, convergent validity, and discriminant validity, and WCST norms adjusted for age and educational level are proposed. This instrument is a reliable and valid tool for the assessment of executive functions. However, as the age- and educational-related effects were demonstrated, these characteristics need to be considered before interpreting WCST scores. Regarding gender, no differences were found. Our results expand the geographical and sociocultural applicability of WCST.

Effects of bioavailable phenolic compounds from Ilex paraguariensis on the brain of mice with lung adenocarcinoma.

Lung carcinoma is one of the most common cancers and has a high mortality. Recently, we showed that it produces neurological paraneoplastic syndrome, with Ilex paraguariensis (IP) extract exerting palliative effects due to its content of phenolic compounds. It is possible, therefore, that these diet agents can arrive at the brain and exert neuroprotection, after the oral intake of IP. Here, the aim was to investigate the protective role of bioavailable IP compounds on the telencephalon and diencephalon in lung adenocarcinoma-bearing BALB/cJ males. Mice aged 2 months were treated for 3 weeks with 0-100 IP mg·kg-1 ·day-1 . HPLC-UV revealed the presence of chlorogenic acid and quercetin in brain regions, liver, and tumour, in an IP dose-dependent manner. Brain was also evaluated histologically, and interleukin-6 was measured by ELISA. Chlorogenic acid was the major compound found in brain, whereas quercetin was observed at the diencephalon to a lesser extent. Both compounds were involved in IP dose-dependent diencephalic interleukin-6 reduction. Histology suggested cellular protection with less apoptosis in chlorogenic-exposed areas. Taken together, chlorogenic acid and quercetin from dietary IP were bioavailable and bioactive in brain, thereby attenuating lung cancer-related neuroinflammation and damage. These findings support plant-based strategies to improve prognosis.

Neuroprotective Effect of Ilex Paraguariensis Intake on Brain Myelin of Lung Adenocarcinoma-Bearing Male Balb/c Mice.

Ilex paraguariensis (IP) is widely consumed as tea with high nutritional value. This plant contains several bioactive phenolic compounds, which are antioxidant and anti-inflammatory. On the other hand, lung adenocarcinoma (LAC) deleteriously involves neoplastic progression, inflammatory paraneoplastic syndromes, and death. Given that brain is a frequent target of this illness, our objective was to determine the neuroprotective effect of IP consumption in LAC-bearing mice. They were orally treated with 50 mg of IP extract/kg/day (IP50) for 3 weeks. Results (phenolic compounds, lipid peroxides, interleukin 6-IL-6-, tumor necrosis factor alpha -TNFα-, and luxol-stained myelination) were compared with respect to untreated controls (C) by the T test. IP50 significantly lowed brain IL-6 (2858.12 ± 57.81 pg g-1 vs. 3801.30 ± 27.34 pg g-1), whereas other variables differed in a less extent. C brains showed demyelination (low luxol-staining contrast between gray and white matters), with IP50 increasing myelination (P < 0.05). In conclusion, LAC deleterious effects on murine brain were prevented by dietary IP, which is an original discovery to develop a nutritional approach against cancer neurological compromise.

Effect of the Aqueous Extract of Lantana grisebachii Stuck Against Bioaccumulated Arsenic-Induced Oxidative and Lipid Dysfunction in Rat Splenocytes.

Arsenic (As) is a worldwide immunotoxic agent that is in contaminated waters and consumed by mammals. Phytotherapy may counteract its harmful effects. Lantana grisebachii Stuck (LG, Verbenaceae) and its extract are proposed as protective, given vvits in vitro bioactivity. The aim was to determine the protective capacity of the aqueous LG extract on splenocytes exposed in vivo to arsenic. Splenocytes were obtained from an arsenicosis model (Wistar rats consuming orally 0 [control; C] or 5 mg/Kg/d of As) that received 0-100 mg/Kg/d of LG extract for 30 days. As content (total reflection X-ray fluorescence), fatty acid profile (gas chromatography), γ-glutamyl transpeptidase activity (Szasz method), peroxides (xylenol orange-based assay), and nitrites (Griess reaction) were then assayed in viable splenocytes. Data were analyzed with ANOVA and the Tukey's test (p < .05). It was observed that the splenocytes contained 2.2 mg/Kg of this elemental arsenic. With γ-glutamyl transpeptidase inhibition and consequent triggering of hydroperoxides (p < .05), it was observed to increase saturated fatty acids and alter lipid profiles. LG treatment avoided damaging effects with values similar to unexposed C (p < .05), and cellular arsenic concentration (p < .0001). In conclusion, the aqueous extract of L. grisebachii counteracted arsenic toxicity in rat splenocytes by preventing its cellular accumulation and induction of lipid and redox disturbances, which may impair immune function.

Differential Potentiation of Retinoic Acid Effects against Human Breast Cancer Cells by Unsaturated Fatty Acids.

Retinoic acid (RA) and unsaturated fatty acids (UFA) are proposed as nutritional anticancer agents. Nonetheless, the activity of their combination on human breast cancer needs further study. Our aim was to evaluate this activity on the MCF-7 and ZR-75-1 cell lines treated with 1 µM RA and 50 µM of γ-linoleic (GLA, ω-6), eicosapentaenoic (EPA, ω-3), oleic (OA, ω-9), or eicosatrienoic (ETA, ω-9) acids. The following cellular responses were compared by ANOVA and Fisher test (P < 0.05): fatty acids, E-cadherin, actin (differentiation), conjugated dienes, γ-glutamyltranspeptidase activity (stress), and viability, which were correlated by partial least squares regression. Although both cell lines responded differentially, RA modified unsaturated fatty acids, increased differentiation, reduced γ-glutamyltranspeptidase, and viability. RA differentiating activity on ZR-75-1 was morphologically enhanced by UFA. Stress induction with γ-glutamyltranspeptidase decrease and conjugated dienes was promoted by ETA in MCF-7, and EPA and OA in ZR-75-1. RA-related reduced viability was potentiated by EPA and OA in both lines. GLA was less active. Therefore, unsaturated fatty acids (ω-3/ω-9) potentiated the multitarget retinoic acid activity against these human breast cancer cells.

Pharmacology and Toxicology of Polyphenols with Potential As Neurotropic Agents in Non-communicable Diseases.

BACKGROUND: The central nervous system (CNS) is involved in organic integration. Nervous modulation via bioactive compounds can modify metabolism in order to prevent systemic noncommunicable diseases (NCDs). Concerning this, plant polyphenols are proposed as neurotropic chemopreventive/ therapeutic agents, given their redox and regulating properties. OBJECTIVE: To review polyphenolic pharmacology and potential neurological impact on NCDs. METHOD: First, polyphenolic chemistry was presented, as well as pharmacology, i.e. kinetics and dynamics. Toxicology was particularly described. Then, functional relevance of these compounds was reviewed focusing on the metabolic CNS participation to modulate NCDs, with data being finally integrated. RESULTS: Oxidative stress is a major risk factor for NCDs. Polyphenols regulate the redox biology of different organic systems including the CNS, which participates in metabolic homeostasis. Polyphenolic neurotropism is determined by certain pharmacological characteristics, modifying nervous and systemic physiopathology, acting on several biological targets. Nonetheless, because these phytochemicals can trigger toxic effects, they should not be recommended indiscriminately. CONCLUSION: Summing up, the modulating effects of polyphenols allow for the physiological role of CNS on metabolism and organic integration to be utilized in order to prevent NCDs, without losing sight of the risks.

Modulation of Fatty Acids and Interleukin-6 in Glioma Cells by South American Tea Extracts and their Phenolic Compounds.

Dietary phenolic compounds are plant metabolites with beneficial effects on the central nervous system. Thus, our aim was to identify anti-inflammatory compounds from South American plants on glia, which regulates neuro-immune response. The compounds were extracted from Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQB), and Ilex paraguariensis (IP) teas and identified by HPLC-DAD-MS. Extracts (0-200 µg/ml) were tested on human T98-G and rat C6 glioma lines. Cellular viability (by the resazurin assay), fatty acid profile (by gas chromatography) and pro-inflammatory interleukin-6 release (IL-6 by ELISA) were determined. Data were analyzed by partial least-square regression to discriminate bioactive compounds. Twenty-one compounds were determined in LG, mainly iridoids, which were linked to ω-3 and ω-6 polyunsaturated fatty acids, but not to IL-6 release. Thirty-one compounds were found in AQB, mostly hydroxybenzoic derivatives, which were positively related to IL-6 release. Twenty-three compounds were identified in IP, including caffeoylquinic derivatives and mainly chlorogenic acid. They increased the ω-7 palmitoleic fatty acid, which was related to IL-6 decrease. These results enhances phytochemical knowledge of widely available plants, and suggest the lipid-related anti-inflammatory activity of IP phenolic compounds, which give nutritional relevance to the tea.

[Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids]. / Modificaciones en el nivel de anión superóxido en leche materna, según la ingesta de flavonoides y carotenoides.

OBJECTIVE: To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. MATERIALS AND METHODS: 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. RESULTS: The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. CONCLUSIONS: Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.

OBJETIVO: Asociar la ingesta de flavonoides y carotenoides con el nivel en leche materna del anión superóxido, como marcador de estrés oxidativo. MATERIAL Y MÉTODOS: Durante el periodo 2013-2015 se estudió a 100 mujeres lactantes de Córdoba (Argentina), dentro los primeros seis meses posparto; se evaluaron sus datos sanitarios, ingesta alimentaria y nivel lácteo del anión con regresión logística múltiple. RESULTADOS: La ingesta de flavonoides, carotenoides provitamínicos y carotenoides no provitaminas fue de 72 (61) mg/día, 1 813 (1657) µg/día y 5 427 (3664) µg/día, respectivamente. El anión se asoció con la ingesta de flavanoles (RM=1.081; IC95 1.001-1.167) y flavanonas (RM=1.025; IC95 1.001-1.048). No se observó este efecto con otros flavonoides ni con los carotenoides. CONCLUSIONES: La ingesta de flavanoles y flavanonas aumenta el riesgo de oxidación láctea, lo cual es relevante para realizar recomendaciones dietéticas.

Modificaciones en el nivel de anión superóxido en leche materna, según la ingesta de flavonoides y carotenoides / Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids

Resumen: Objetivo: Asociar la ingesta de flavonoides y carotenoides con el nivel en leche materna del anión superóxido, como marcador de estrés oxidativo. Material y métodos: Durante el periodo 2013-2015 se estudió a 100 mujeres lactantes de Córdoba (Argentina), dentro los primeros seis meses posparto; se evaluaron sus datos sanitarios, ingesta alimentaria y nivel lácteo del anión con regresión logística múltiple. Resultados: La ingesta de flavonoides, carotenoides provitamínicos y carotenoides no provitaminas fue de 72 (61) mg/día, 1 813 (1657) µg/día y 5 427 (3664) µg/día, respectivamente. El anión se asoció con la ingesta de flavanoles (RM=1.081; IC95 1.001-1.167) y flavanonas (RM=1.025; IC95 1.001-1.048). No se observó este efecto con otros flavonoides ni con los carotenoides. Conclusiones: La ingesta de flavanoles y flavanonas aumenta el riesgo de oxidación láctea, lo cual es relevante para realizar recomendaciones dietéticas.

Abstract: Objective: To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. Materials and methods: 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. Results: The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. Conclusions: Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.

Delay of Lung Adenocarcinoma (LAC-1) Development in Mice by Dietary Oleic Acid.

Lung cancer is the leading cause of death by cancer, and is a major sanitary concern worldwide. Some nutrients, such as ω-9 fatty acids, have been proposed as anticancer agents. Thus, an olein-enriched diet was assayed in a murine model of lung adenocarcinoma (LAC-1) to evaluate neoplastic and paraneoplastic evolution in BALB/c mice. The organic assimilation of dietary fatty acids was confirmed in liver by gas chromatography. This experimental oleic acid-containing diet increased animal survival and tumour latency (analysed by the Kaplan-Meier method), improving neoplastic evolution and general status, with weak effects on the paraneoplastic syndrome (thymus atrophy, splenomegaly, splenocyte response to mitogen, blood anaemia, and leucocytosis). Tumour lipid oxidation was not involved. Thus, diet enrichment with olein, a natural source of the ω-9 oleic acid, significantly delayed progression of LAC-1 and increased tumour latency and mice survival. These results support its use in nutritional management of cancer, with further studies being encouraged.

Immunotoxicological effects of arsenic bioaccumulation on spatial metallomics and cellular enzyme response in the spleen of male Wistar rats after oral intake.

Arsenic (As) is a worldwide environmental contaminant, which compromises immunity and causes various associated disorders. To further investigate its immunotoxicity, male Wistar rats were exposed to 100ppm of sodium arsenite (inorganic AsIII) in drinking water for 2 months. Given that metals are significant immune regulators, their content and distribution were analysed in spleen tissues, to then evaluate subsequent changes of redox enzyme responses in spleen parenchyma cells (splenocytes). X-ray fluorescence spectrometry demonstrated As accumulation in both white and red pulps (p<0.005), and As-related pulp-dependent modifications of the content of Cu, Ca, Zn and Fe (p<0.01). Correlational path analysis revealed direct effects of As on their spatial distribution (Cu: -0.76, Ca: -0.61, Zn: 0.38; p<0.02). As-exposed splenocytes showed ɣ-glutamyltranspeptidase inhibition, peroxidase induction, and variable responses of nitric oxide synthase (p<0.05). Concanavalin A-treated splenocytes (T cell mitogen) were more susceptible in vitro to these As-related enzymatic changes than those treated with lipopolysaccharide (B cell mitogen) (p<0.05). The study thus established the impact of As bioaccumulation on metallic spatial homeostasis in the spleen, and then identified enzymatic dysfunctions in splenocytes. This suggested that arsenic disrupts biometal-dependent immune pathways and redox homeostasis, with mitogen exposure modifying the toxicological response.

Effect of arsenite on nitrosative stress in human breast cancer cells and its modulation by flavonoids.

Arsenic (As) is used in the treatment of leukemia and breast cancer due to its oxidative cytotoxic action. However, it is also toxic to normal cells. One proposed anticancer mechanism induced by As might be nitrosative stress (NS). It is believed that antioxidant flavonoids in combination with As might reduce its toxic action on normal cells without interfering with its antitumor action. In the present study, we evaluated the antineoplastic potential of As on breast human cancer lines MCF-7 and ZR-75-1 treated with redox-modulating flavonoids, such as quercetin (Q) and silymarin (S). Even though both cell lines differed about their oxidative responsiveness, their viability was decreased by NS induction through γ-glutamyltranspeptidase inhibition. Arsenic triggered NS in both MCF-7 and ZR-75-1 cultures, with the formers more sensitive without recovering their pre-treatment capacity. ZR-75-1 cells maintained their antioxidant status, whereas MCF-7 ones treated with S, As, and As + Q did not. Silymarin did not interfere with the described As bioactivity. NS was an anticancer mechanism exerted by As depending on the redox cellular response that could be differentially modified by dietary antioxidants. Hence, it is worthwhile to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy, especially when using As.

Development of an Antioxidant Phytoextract of Lantana grisebachii with Lymphoprotective Activity against In Vitro Arsenic Toxicity.

Phytochemicals have been presumed to possess prophylactic and curative properties in several pathologies, such as arsenic- (As-) induced immunosuppression. Our aim was to discover a lymphoprotective extract from Lantana grisebachii Stuck. (Verbenaceae) (LG). We assessed its bioactivity and chemical composition using cell-based assays. Fractions produced from a hexane extract acutely induced nitrite formation in T-activated cell cultures (P < 0.0001). Water extraction released a fraction lacking nitrite inducing activity in both lymphocyte types. Aqueous LG was found to be safe in proliferated and proliferating cells. The infusion-derived extract presented better antioxidant capacity in proportion to phenolic amount in lymphocytes (infusive LG-1i at 100 µ g/mL), which protected them against in vitro As-induced lymphotoxicity (P < 0.0001). This infusive LG phytoextract contained 10.23 ± 0.43 mg/g of phenolics, with 58.46% being flavonoids. Among the phenolics, the only predominant compound was 0.723 mg of chlorogenic acid per gram of dry plant, in addition to 10 unknown minor compounds. A fatty acid profile was assessed. It contained one-third of saturated fatty acids, one-third of ω 9, followed by ω 6 (~24%) and ω 3 (~4%), and scarce ω 7. Summing up, L. grisebachii was a source of bioactive and lymphoprotective compounds, which could counteract As-toxicity. This supports its phytomedical use and research in order to reduce As-related dysfunctions.

Arsenic immunotoxicity and immunomodulation by phytochemicals: potential relations to develop chemopreventive approaches.

Arsenic (As) contaminates drinking water worldwide, and As exposure, hypersensitivity and deficiency are involved in the immunopathogenesis of various health problems. Its chemoprevention thus has a high health impact. Given its oxidative potential, antioxidant compounds are good candidates to counteract arsenic's deleterious effects on humans. Phytochemicals (e.g., phenolics, carotenoids, etc.) act through free radical chelation activity and regulation of cellular targets. Consequently, they are appropriate for developing anti-As strategies derived from plants, and Argentinean flora is rich in useful species. Several molecular pathways involved in immune regulation are at the same time targets of exogenous agents, and oxidative stress itself is a modulating phenomenon of immunity. Since xenohormesis has been described as the organic enhancement of resistance to stress conditions (e.g., oxidation, pollution, etc.) by consuming xenobiotics, immunoxenohormesis implies also defense improvement. This review focuses on recent patents on the development of vegetable redox-related immunomodulating agents, which might be applied in As-induced dysfunctions, with their scientific basis being reviewed.

Anti-breast cancer activity of curcumin on the human oxidation-resistant cells ZR-75-1 with gamma-glutamyltranspeptidase inhibition.

Since curcumin, a polyphenol extracted from the rhizomes of Curcuma longa L. (Zingiberaceae), has been proposed for breast cancer chemoprevention, the aim of the present work was to determine if it had anti-tumour effects on mammary cells which are resistant to oxidative damage. ZR-75-1 cells were treated with curcumin and copper(II) sulphate in order to evaluate cell death and gamma-glutamyltranspeptidase (GGTP) activity. Curcumin was cytotoxic in a dose-dependent manner (loss of viability with lactate-dehydrogenase release) with apoptotic effects on ZR-75-1 cells. Also, curcumin displayed an antioxidant effect only on the copper-oxidized cells. The GGTP activity was decreased in a dose-dependent manner by curcumin, with the changes in this parameter accounting for neoplastic inhibition (direct relation between the enzyme activity and cellular viability). Summing up, our results suggest that curcumin induced apoptosis in ZR-75-1 with an antioxidant activity performed on those treated with copper(II) sulphate, which should be explored more thoroughly with the involvement of the GGTP enzyme activity as biomarker of their malignancy.