Growth Of Mammary Tumors In Mice Research Articles

Long-term high-fat diet limits exercice benefits on mammary tumor growth in mice

Long-term high-fat diet limits exercice benefits on mammary tumor growth in mice

Robust eIF4B levels undermine invasive growth and immune evasion mechanisms in murine triple negative breast cancer models.

Abstract Dysregulated protein synthesis is seen in many aggressive cancers, including metastatic breast cancer. However, the specific contributions of certain translation initiation factors to in vivo disease remain undefined. This is particularly true of eIF4B, an RNA-binding protein and cofactor of the RNA helicase eIF4A and associated eIF4F cap-binding complex. While eIF4A, eIF4G, and eIF4E are known to contribute to the progression of many cancer types, the role played by eIF4B in breast cancer remains relatively unclear. We therefore explored how naturally divergent and experimentally modulated eIF4B levels impact tumor growth and progression in murine triple negative breast cancer (TNBC) models. Surprisingly, we found that higher eIF4B levels in mouse and human breast cancers were associated with less aggressive phenotypes. shRNA-mediated eIF4B knockdown in TNBC lines failed to markedly alter proliferation and global translation in cells grown in vitro and only modestly hindered primary mammary tumor growth in mice. However, eIF4B knockdown significantly enhanced invasive growth in vitro and exacerbated both tumor burden and mortality relative to nontargeting shRNA controls in a model of metastatic disease. Deposited patient data reinforced a link between high eIF4B levels and better outcomes. Interestingly, in vitro and in vivo studies associated low eIF4B expression with more formidable immune evasion. These findings suggest that eIF4B levels impact metastatic disease in part through immunomodulatory mechanisms beyond the factor’s traditional role supporting eIF4/F directed translation. Future studies should explore the impact of these findings for personalizing treatment decisions and developing future therapies.

Antitumor effect of selenium-rich Brazil nuts and selenomethionine dietary supplementation on pre-existing 4T1 mammary tumor growth in mice.

Selenium (Se) is an essential micronutrient known to play an important role in the antioxidant system that can potentially influence tumor growth. We aimed to investigate the effects of dietary Se supplementation after detection of 4T1 mammary tumor growth in BALB/c mice. Thirty female mice received subcutaneous inoculation of 4T1 cells. After five days, all animals presenting palpable tumors were randomly assigned to three groups: a control group (Se-control) receiving a diet with adequate Se (0.15 mg/kg) and two other groups that received Se-supplemented diets (1.4 mg/kg of total Se) with either Brazilian nuts (Se-Nuts) or selenomethionine (SeMet). Data were assessed by either One or Two-way ANOVA followed by Tukey's HSD or Bonferroni's post hoc tests, respectively. Both Se-supplemented diets reduced tumor volume from the thirteenth day of feeding compared with the Se-adequate (control) diet (p < 0.05). The SeMet group presented a higher Se blood concentration (p < 0.05) than the Se-control group, with the Se-Nuts group presenting intermediate values. Selenoprotein P gene expression in the liver was higher in the Se-Nuts group than in the Se-control group (p < 0.05), while the SeMet group presented intermediate expression. Dietary Se supplementation, starting after detection of 4T1 palpable lesions, reduced tumor volume in mice.

Abstract P5-08-09: Characterization of the Rac/Cdc42 inhibitor MBQ-168 as an anti-cancer compound

Abstract Metastasis continues to be the primary cause of cancer-related death in women with breast cancer, needing targeted therapies to inhibit this process. Therefore, we developed inhibitors targeting the homologous Rho GTPases Rac1 and Cdc42, which direct the actin cytoskeletal changes required for cell migration/invasion; and thus, metastasis. We characterized the potent inhibitor, MBQ-167 that blocks both Rac1 and Cdc42 at IC50s 103 nM and 78 nM, respectively, in human HER2 (+) and triple-negative breast cancer (TNBC) cells. Consequently, MBQ-167 inhibits tumor growth and metastasis by ~90% in pre-clinical mouse models of breast cancer (Humphries-Bickley, et al., 2017). To improve the activity and solubility of MBQ-167, we synthesized a panel of derivatives, maintaining the 9-ethyl-3-(1H-1,2,3-triazol-1-yl)-9H-carbazole as the core for each derivative. Of the derivatives tested, MBQ-168 demonstrated improved solubility and comparable efficacy. Similar to MBQ-167, MBQ-168 induced actin cytoskeletal disintegration, cell rounding, and detachment to ultimately undergo anoikis. In 120hrs, MBQ-168 significantly inhibited the viability of MDA-MB-231 at a GI50 of 228nM and HER2+ MDA-MB-435 cells with a GI50 of 137 nM, without affecting the viability of Human Mammary Epithelial Cells (HMEC). In apoptosis assays, MBQ-168 treatment, at 500nM for 48 hrs, demonstrated a similar response to MBQ-167 by &amp;gt;4-fold increase in Caspase 3/7 activity in HER2 (+), and MDA-MB-231 and MDA-MB-468 TNBC cells. In wound healing assays, MBQ-168 also responded similar to MBQ-167 by a ~80% inhibition of breast cancer cell migration at 250nM and 500nM for 24hrs. Moreover, as quantified from Rac1.GTP pulldown assays, following 250nM treatment for 24hrs, MBQ-168 inhibited Rac1 activation in the attached cell population by ~70%, and in the detached cell population by ~100%, demonstrating a potent inhibition of Rac1 activation. In a preliminary study for relative efficacy in mice, MBQ-168 significantly reduced HER2+ MDA-MB-435 mammary tumor growth (~90%) at 5mg/kg BW via IP administration. In conclusion, MBQ-168 is an effective Rac inhibitor that reduces breast cancer cell viability, induces apoptosis, and inhibits breast cancer cell migration, actin cytoskeletal extensions, and Rac1 activation to result in a drastic reduction in mammary tumor growth in mice. We predict that the increased solubility of MBQ-168 will make it more bioavailable than MBQ-167. Thus, we have demonstrated that small structural modifications of MBQ-167 can affect the cytotoxic activity of carbazole derivatives with potential as anti-cancer drugs, and as tools to block Rac/Cdc42 activities in biological systems. Citation Format: Julia Medina, Tatiana Matos, Luis Velazquez, Michael Rivera, Ailed Cruz-Collazo, Eliud Hernandez, Cornelis Vlaar, Suranganie Dharmawardhane. Characterization of the Rac/Cdc42 inhibitor MBQ-168 as an anti-cancer compound [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-09.

Influence of normal mammary epithelium on breast cancer progression: the protective role of early pregnancy

The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue. In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry. Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway. These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice.

Abstract 3493: Soluble ALK4 extracellular domain antagonizes the cancer/stem cell phenotype caused by Nodal and Cripto signaling in mammary epithelia

Abstract We recently determined that a fraction of cells in a highly enriched fetal mammary stem cell pool expresses the oncofetal protein Cripto and its receptor/co-factor GRP78 on their surfaces. Cripto is a GPI-anchored protein important for embryonic stem cell self-renewal and developmental plasticity. It is also selectively overexpressed in multiple human tumors including ∼80% of human breast tumors. Cripto overexpression increases cellular proliferation, invasion and migration in vitro and promotes mammary tumor growth in mice. Cripto functions as an obligatory co-receptor for Smad2/3 activation by the TGF-β superfamily member Nodal but attenuates activin-A and TGF-β1 signaling and the cytostatic effects of these ligands on human mammary epithelial cells. Cripto can be secreted from cells and soluble forms activate Src, ras/raf/MAPK and PI3K/Akt pathways. We recently identified the HSP70 family member GRP78 as a cell surface receptor/co-factor that is required for Cripto signaling via TGF-β and Src/MAPK/PI3K pathways. Here, we developed a soluble and highly specific Cripto antagonist based on the extracellular domain of the Activin/Nodal Type I serine/threonine kinase receptor ALK4 (sALK4-ECD). We tested the ability of this antagonist to block Cripto signaling via TGF-β and Src/MAPK/PI3K pathways in oncogenic and stem cell phenotypes in mammary epithelial cells and breast cancer cell lines. The sALK4-ECD protein dose-dependently and specifically inhibited 125I-Cripto binding to 293T cells transfected with full length ALK4. In addition, sALK4-L75A-Fc blocked 125I-Cripto binding to native human mammary epithelial MCF10A cells. sALK4-ECD inhibited Cripto-dependent Nodal signaling in 293T cells and inhibited Nodal-induced Smad2 phosphorylation in native NCCIT cells. sALK4-ECD also blocked Cripto-induced PI3K activation, cell proliferation and migration in MCF10A cells. Cripto and Nodal signaling had profound effects on MCF10A growth in suspension and mammosphere reseeding capacity that were also inhibited by sALK4-ECD. We evaluated Nodal/Cripto signaling in cancer cell lines and primary fetal mammary stem cells and tested the efficacy of sALK-ECD mediated suppression of Nodal and Cripto effects in vitro and in vivo. These studies were designed to test if Cripto represents a functional cell surface marker of normal stem cells and/or the cells that initiate or perpetuate breast cancers. Our results point to distinct roles for Cripto and Nodal/Cripto signaling in promoting the oncogenic phenotype via activation of Smad2/3 and PI3K pathways, and support a role for Cripto antagonism such as that afforded by sALK4-ECD as a potential therapeutic strategy for the treatment of human disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3493. doi:1538-7445.AM2012-3493

P2-03-01: Genetic Reduction of Circulating Insulin-Like Growth Factor (IGF)-1 Differentially Impacts the Effects of Diet-Induced Obesity and Calorie Restriction on Mammary Tumor Progression.

Abstract Background: Epidemiological evidence suggests that obesity worsens breast cancer prognosis in pre- and postmenopausal women. Previously we demonstrated that diet-induced obese (DIO) mice and rats have higher circulating levels of IGF-1 and enhanced mammary tumor burden compared to normoweight controls. In contrast, we have found in several mouse models that a 30% calorie restricted (CR) diet regimen reduced serum IGF-1 levels and decreased mammary tumor growth. The present study investigated the effects of CR and DIO on mammary tumor growth in mice with normal serum levels of IGF-1 (wild-type) or mice with reduced circulating levels of IGF-1 (LID). Our goal was to identify new targets and strategies (with a focus on the IGF-1 pathway) for breaking the obesity-breast cancer link, which is important given the high prevalence of obesity in the U.S., and the strong association between obesity and breast cancer. Materials and Methods: Virgin female liver-specific IGF-1-deficient (LID) and wild-type (FVB/NCr) mice (10-12 weeks of age) were randomized (n=10-14 per group) to receive: control diet (modified AIN-76A), a 30% CR regimen, or a DIO regimen (60 kcal% fat diet). Mice consumed the experimental diets for 11 to 15 weeks prior to orthotopic injection (4th mammary fat pad) of Met-1fvb2murine mammary tumor cells derived from a polyoma middle-T antigen transgenic mouse mammary tumor. Transplanted tumors were allowed to grow for 4 weeks and tumor volume was measured by electronic calipers biweekly. Mice were then killed, serum was collected and stored at −80C, and tumors were excised, weighed and either formalin-fixed, paraffin-embedded or flash-frozen. Results: Using the LID mouse model of IGF-1 deficiency, this study established that decreased circulating IGF-1 (relative to wildtype mice) dramatically reduces Met-1fvb2 mammary tumor growth regardless of diet treatment (P=0.034). We also showed in LID mice that CR (44 +/− 15.6 mm3), relative to control diet (89 +/− 33 mm3) has no significant effect on Met-1fvb2 tumor growth, suggesting nearly all of the suppressive effects of CR on tumor growth (at least in the Met-1fvb2 model), can be explained by reduced systemic IGF-1. In contrast, while most of the DIO effect on tumor growth was ablated in the LID mice (332 +/− 104 mm3) vs. wild-type mice (3130 +/− 421 mm3), tumor growth in LID/DIO mice was significantly higher than LID/control mice (89 +/− 33, P=0.006) despite no change in IGF-1 levels, suggesting that a mechanism independent of IGF-1 contributes to some of the effects of DIO on Met-1fvb2 mammary tumor growth. Within LID mice, serum insulin, resistin and adiponectin were not modified by the CR or DIO diet. Discussion: We conclude that components of the IGF-1 pathway represent promising mechanistic targets for mimicking the anticancer effects of CR and breaking the obesity-breast cancer link. However, there are likely other mechanisms independent of IGF-1 that contribute to the breast tumor enhancing effects of DIO and that need to be defined. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-03-01.

Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity

Obesity is an established risk and progression factor for postmenopausal breast cancer. Interventions to decrease caloric intake and/or increase energy expenditure beneficially impact tumor progression in normoweight humans and animal models. However, despite the increasingly high global prevalence of obesity, the effects and underlying mechanisms of these energy balance modulating interventions are poorly characterized in obese individuals. The goal of this study was to better characterize the mechanism(s) responsible for the link between energy balance and breast cancer progression in the postmenopausal obesity context. We compared the effects of calorie restriction (CR), treadmill exercise (EX), and mammalian target of rapamycin (mTOR inhibitor) treatment on body composition, serum biomarkers, cellular signaling, and mammary tumor growth in obese mice. Ovariectomized C57BL/6 mice were administered a diet-induced obesity regimen for 8 weeks, then randomized into three treatment groups: control (semipurified diet fed ad libitum, maintained the obese state); 30% CR (isonutrient relative to control except 30% reduction in carbohydrate calories); and EX (control diet fed ad libitum plus treadmill exercise). Mice were implanted with syngeneic MMTV-Wnt-1 mammary tumor cells at week 12. Rapamycin treatment (5 mg/kg every 48 h) started at week 14. Tumors were excised at week 18. CR and rapamycin (but not EX) significantly reduced final tumor weight compared to control. In follow-up analysis, constitutive activation of mTOR ablated the inhibitory effects of CR on Wnt-1 mammary tumor growth. We conclude that mTOR inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR and break the obesity-breast cancer progression link.

Abstract A75: Calorie restriction and rapamycin, but not exercise, inhibit mammary tumor growth in a mouse model of postmenopausal obesity

Abstract Obesity is a well-established risk factor for postmenopausal breast cancer and is associated with poor outcomes in both premenopausal and postmenopausal women. Given that approximately one third of the US population is obese, interventions to reverse the detrimental effects of obesity on breast cancer progression are urgently needed. The molecular target of Rapamycin (mTOR) modulates pathways regulating energy balance and cell growth. Therefore, agents that target the mTOR pathway are promising for breaking the obesity-breast cancer link. Here, we directly compared the two most recommended strategies for reversing obesity, calorie restriction (CR) and exercise (EX), and a well-established mTOR inhibitor (rapamycin) on mammary tumor growth and metabolic profiles in obese mice. Ovariectomized C57BL/6 mice were administered a diet-induced obesity regimen for 8 weeks, then randomized into 3 diet or exercise treatment groups: Control (AIN-76A diet fed ad libitum to maintain the obese state, n=30); 30% CR (70% of the carbohydrate calories but otherwise isonutrient relative to control, n=15); EX (control diet fed ad libitum plus treadmill exercise regimen, n=15). Mice were orthotopically implanted (4th mammary gland) with syngeneic MMTV-Wnt-1 mammary tumor cells at week 12. Of the 30 mice in the control group, 15 received rapamycin (5mg/kg, administered ip every 48hrs) starting at week 14. All other mice received vehicle treatment (saline, administered ip every 48 hrs) starting at week 14. Tumors were excised at week 18. Final tumor weights from mice in the CR (0.043 ± 0.007 g) and rapamycin (0.072 ± 0.010 g) groups, but not EX (0.380 ± 0.072 g) group, were significantly reduced compared to control (0.390 ± 0.066 g). The crucial role of mTOR in the link between obesity and breast cancer progression was confirmed in a follow up study where constitutive activation of mTOR (mTOR) ablated the inhibitory effects of CR on mammary tumor growth. CR failed to reduce tumor weight in mice injected with cells transfected with mTOR (0.38 ± 0.05 g), compared to control (0.55 ± 0.08 g). Transfection effect bias was discarded since CR significantly reduced weight of tumors (0.29 ± 0.03 g) in mice injected with cells transfected with WT mTOR, compared to control (0.62 ± 0.12 g). We conclude that mTOR inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR and break the obesity-breast cancer progression link. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A75.

Breast cancer therapy with IL-25

A U.S.-Taiwan team has shown that the proinflammatory cytokine IL-25 exerts potent cytotoxic effects in breast cancer cells and decreases mammary tumor growth in mice. The researchers and an undisclosed company will collaborate to develop systems for delivering IL-25 or its mimetics directly to tumors.

Interferon γ-Induced Human Guanylate Binding Protein 1 Inhibits Mammary Tumor Growth in Mice

Interferon gamma (IFN-gamma) has recently been implicated in cancer immunosurveillance. Among the most abundant proteins induced by IFN-gamma are guanylate binding proteins (GBPs), which belong to the superfamily of large GTPases and are widely expressed in various species. Here, we investigated whether the well-known human GBP-1 (hGBP-1), which has been shown to exert antiangiogenic activities and was described as a prognostic marker in colorectal carcinomas, may contribute to an IFN-gamma-mediated tumor defense. To this end, an IFN-independent, inducible hGBP-1 expression system was established in murine mammary carcinoma (TS/A) cells, which were then transplanted into syngeneic immune-competent Balb/c mice. Animals carrying TS/A cells that had been given doxycycline for induction of hGBP-1 expression revealed a significantly reduced tumor growth compared with mock-treated mice. Immunohistochemical analysis of the respective tumors demonstrated a tightly regulated, high-level expression of hGBP-1. No signs of an enhanced immunosurveillance were observed by investigating the number of infiltrating B and T cells. However, hemoglobin levels as well as the number of proliferating tumor cells were shown to be significantly reduced in hGBP-1-expressing tumors. This finding corresponded to reduced amounts of vascular endothelial growth factor A (VEGF-A) released by hGBP-1-expressing TS/A cells in vitro and reduced VEGF-A protein levels in the corresponding mammary tumors in vivo. The results suggest that hGBP-1 may contribute to IFN-gamma-mediated antitumorigenic activities by inhibiting paracrine effects of tumor cells on angiogenesis. Consequently, owing to these activities GBPs might be considered as potent members in an innate, IFN-gamma-induced antitumoral defense system.

Activated Abl kinase inhibits oncogenic transforming growth factor‐β signaling and tumorigenesis in mammary tumors

Transforming growth factor-beta (TGF-beta) is a ubiquitous cytokine with dual roles in tumor suppression and promotion, and these dichotomous functions have frustrated the development of therapies targeting oncogenic signaling by TGF-beta. In comparison, Abl is well established as an initiator of hematopoietic cancers; however, a clear role for Abl in regulating solid tumor development remains elusive. Here, we investigated the role of Abl in TGF-beta-mediated epithelial-mesenchymal transition (EMT) in normal and metastatic mammary epithelial cells (MECs). In doing so, we identified Abl as an essential regulator of MEC morphology and showed that Abl inactivation was sufficient to induce phenotypic and transcriptional EMT in normal MECs. Increasing Abl activity in metastatic MECs resulted in their complete morphological reversion, restored their cytostatic response to TGF-beta, and blocked their secretion of matrix metalloproteinases induced by TGF-beta. Constitutively active Abl expression blocked TGF-beta-responsive mammary tumor growth in mice, while Imatinib therapy afforded no clinical benefit in mice bearing mammary tumors. Collectively, this investigation establishes Abl as a potent mediator of MEC identity, and as a suppressor of oncogenic TGF-beta signaling during mammary tumorigenesis. Notably, our findings strongly caution against the use of pharmacological Abl antagonists in the treatment of developing and progressing mammary tumors.

Letters to the Editor

The Journal of Alternative and Complementary MedicineVol. 10, No. 5 Letters to the EditorPublished Online:9 Nov 2004https://doi.org/10.1089/acm.2004.10.737AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byEffects of noni on cellular viability and osteogenic differentiation of gingiva‑derived stem cells demonstrated by RNA sequencing and quantitative PCR8 November 2021 | Experimental and Therapeutic Medicine, Vol. 23, No. 1The Effect of Corrected Inflammation, Oxidative Stress and Endothelial Dysfunction on Fmd Levels in Patients with Selected Chronic Diseases: A Quasi-Experimental Study2 June 2020 | Scientific Reports, Vol. 10, No. 1Systematic Review on Anticancer Potential and other Health Beneficial Pharmacological Activities of Novel Medicinal Plant Morinda citrifolia (Noni)International Journal of Pharmacology, Vol. 9, No. 8Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 TransgeneEvidence-Based Complementary and Alternative Medicine, Vol. 2012 Volume 10Issue 5Oct 2004 InformationCopyright 2004, Mary Ann Liebert, Inc.To cite this article:Letters to the Editor.The Journal of Alternative and Complementary Medicine.Oct 2004.737-742.http://doi.org/10.1089/acm.2004.10.737Published in Volume: 10 Issue 5: November 9, 2004PDF download

Dietary Lutein from Marigold Extract Inhibits Mammary Tumor Development in BALB/c Mice

High levels of dietary lutein can inhibit mammary tumor growth in mice. However, the antitumor effect of low levels of dietary lutein on mammary tumors is unavailable. Female BALB/c mice and the WAZ-2T (−SA) mammary tumor cell line were used in two experiments. A preliminary tumor cell dose titration study (Experiment 1) was designed to determine the inoculation dose to produce ∼65% tumor incidence. Mice (n = 10/dose) were inoculated with 0 to 1 × 106 tumor cells in the right inguinal mammary fat pad. A tumor cell load of 2.5 × 103 cells/inoculation produced ∼65% tumor incidence. This dose was used in a subsequent study (Experiment 2) of the efficacy of dietary lutein against mammary tumor development. Mice (n = 20/treatment) were fed a semisynthetic diet containing 0, 0.002, 0.02, 0.2 or 0.4% lutein from marigold extract. After 14 d, all mice were inoculated with 2.5 × 103 tumor cells, and tumor growth was measured daily for 70 d at which time blood, liver, spleen and tumors were obtained. Lutein + zeaxanthin uptake increased dose-dependently (P < 0.05) with dietary lutein levels from 0 to 0.02% (spleen) or 0.2% (plasma, liver and tumor). Low levels (0.002 and 0.02%) of dietary lutein lowered (P < 0.05) mammary tumor incidence, tumor growth and lipid peroxidation, and increased tumor latency, whereas higher dietary levels (0.2 or 0.4%) were less effective. Therefore, very low amounts of dietary lutein (0.002%) can efficiently decrease mammary tumor development and growth in mice.