Anthracene Induced Breast Cancer Research Articles

Chemoprotective Effect of Bryodulcosigenin against 7,12-Dimethylbenz(a)anthracene-induced Breast Cancer via Suppression of Inflammation, Oxidative Stress, and Apoptosis

Chemoprotective Effect of Bryodulcosigenin against 7,12-Dimethylbenz(a)anthracene-induced Breast Cancer via Suppression of Inflammation, Oxidative Stress, and Apoptosis

Efficacy of Jasminum subtriplinerve Extract against 7,12-Dimethylbenz[a]anthracene-Induced Cancer in Mice.

Jasminum subtriplinerve Blume tea is a traditional Vietnamese medicine used to treat impetigo, menstruation issues, and painful menstrual hematometra. Previous studies have shown that extracts and isolated compounds from J. subtriplinerve possess diverse pharmacological properties, such as antioxidant, antibacterial, and antidiabetic effects. However, their potential anticancer effects and underlying mechanisms of action have not been clear. Here, we examined the effects of J. subtriplinerve extracts against three human cancer cell lines. We also conducted in vivo analyses using a mouse model of 7,12-dimethylbenz[a]anthracene-induced breast cancer, including an investigation of changes in histological sections. The effect of the J. subtriplinerve ethyl acetate fraction on cytokine levels (IL-2, PGE2, TNF-α) in serum was determined using ELISA kits. Results showed that the EtOAc fraction had the highest anti-proliferative activity (IC50 = 13.7 mg/ml) against the breast cancer (MCF-7) cell line, while the BuOH and water fractions did not show any anticancer effects. Additionally, the EtOAc fraction at a dose of 14.4 mg/kg was able to elevate IL-2 levels and suppress the expression of PGE2 in the serum of mice. A remarkable decrease in the percentage of death and tumor incidence in mice was achieved following treatment with the EtOAc fraction at a dose of 14.4 mg/kg. No abnormal parameters in blood were observed in the J. subtriplinerve treatment groups. These results suggest that J. subtriplinerve, when used as tea or a functional food, is nontoxic and has clear chemopreventive effects against breast cancer.

Redox-Sensitive Poly(lactic-co-glycolic acid) Nanoparticles of Palbociclib: Development, Ultrasound/Photoacoustic Imaging, and Smart Breast Cancer Therapy.

Breast cancer is one of the leading causes of mortality in women globally. The efficacy of breast cancer treatments, notably chemotherapy, is hampered by inadequate localized delivery of anticancer agents to the tumor site, resulting in compromised efficacy and increased systemic toxicity. In this study, we have developed redox-sensitive poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the smart delivery of palbociclib (PLB) to breast cancer. The particle size of formulated PLB@PLGA-NPs (nonredox-sensitive) and RS-PLB@PLGA-NPs (redox-sensitive) NPs were 187.1 ± 1.8 nm and 193.7 ± 1.5 nm, respectively. The zeta potentials of nonredox-sensitive and redox-sensitive NPs were +24.99 ± 2.67 mV and +9.095 ± 1.87 mV, respectively. The developed NPs were characterized for morphological and various physicochemical parameters such as SEM, TEM, XRD, DSC, TGA, XPS, etc. The % entrapment efficiency of PLB@PLGA-NPs and RS-PLB@PLGA-NPs was found to be 85.48 ± 1.29% and 87.72 ± 1.55%, respectively. RS-PLB@PLGA-NPs displayed a rapid drug release at acidic pH and a higher GSH concentration compared to PLB@PLGA-NPs. The cytotoxicity assay in MCF-7 cells suggested that PLB@PLGA-NPs and RS-PLB@PLGA-NPs were 5.24-fold and 14.53-fold higher cytotoxic compared to the free PLB, respectively. Further, the cellular uptake study demonstrated that redox-sensitive NPs had significantly higher cellular uptake compared to nonredox-sensitive NPs and free Coumarin 6 dye. Additionally, AO/EtBr assay and reactive oxygen species analysis confirmed the superior activity of RS-PLB@PLGA-NPs over PLB@PLGA-NPs and free PLB. In vivo anticancer activity in dimethyl-benz(a)anthracene-induced breast cancer rats depicted that RS-PLB@PLGA-NPs was highly effective in reducing the tumor size, hypoxic tumor, and tumor vascularity compared to PLB@PLGA-NPs and free PLB. Further, hemocompatibility study reveals that the developed NPs were nonhemolytic to human blood. Moreover, an in vivo histopathology study confirmed that both nanoparticles were safe and nontoxic to the vital organs.

Effects of Aia tempayang on total antioxidant capacity and malondialdehyde level against 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

Breast cancer occurs due to the abnormal growth and proliferation of cells derived from breast tissue that is caused by continuous stimulation by carcinogenic factors. Breast cancer can be prevented by consuming food that contains antioxidants, such as Aia tempayang. Aia tempayang is a traditional drink originating from West Sumatra. It is made from sappan wood, pangdahai, and basil seeds. Each of its ingredients contains compounds such as antioxidants that can help prevent breast cancer. This study aimed to prove the effectiveness of the administration of Aia tempayang in preventing breast cancer in rats induced by 7,12-dimethylbenz(a)anthracene (DMBA). Healthy female Sprague Dawley rats (35 days old, 150 – 300 g, n = 30) were divided into five groups (n = 6 rats/ group): normal control group (K1); control groups induced by DMBA without treatment (K2); treatment group induced by DMBA + sappan wood 0.072 g + pangdahai 0.012 g + basil seeds 0.045 g (X1); treatment group induced by DMBA + sappan wood 0.144 g + pangdahai 0.024 g + basil seeds 0.09 g (X2); and treatment group induced by DMBA + sappan wood 0.288 g + pangdahai 0.048 g + basil seeds 0.18 g (X3). All rats were gently palpated in the mammary glands to detect the development of any abnormal mass after 5 weeks of intervention. A significant increase in TAC levels was observed in the X1, X2, and X3 groups compared with the K2 group after the treatments (p = 0.000). In addition, there was a significant decrease in the MDA levels in the X1, X2, and X3 groups compared with the K2 group after the treatments (p = 0.000). In conclusion, the administration of Aia tempayang increases the TAC levels and decreases the MDA levels in breast cancer rats induced by DMBA.

The Combined Effects of Dietary Fat and Estrogen on Survival, 7,12-Dimethylbenz(a)anthracene-Induced Breast Cancer and Prolactin Metabolism in Rats

The relationships between dietary fact concentration (10 or 40% of energy), fat source (corn oil or beef tallow) and estrogen (control, ovariectomy or ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis and survival in rats were studied in a 2 × 2 × 3 factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h later: sham ovariectomy (control), overiectomy (OVX) or ovariectomy with a subcutaneous estrogen implant (OVX+E). Each group was subdivided into dietary groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX+E rats exhibited serum estrogen concentrations in excess of physiologic values. Survival at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX+E 13%. Mortality in controls was doubled by feeding a high fat diet; no diet effect was detected in OVX or OVX+E rats. Palpable tumors developed in 74, 14 and 60% of control, OVX and OVX+E rats, respectively. High fat diets approximately doubled the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in control, OVX and OVX+E rats, respectively. The odds of having any tumor, and adenocarcinoma of an adenoma were multiplied by 3.6, 2.8 and 2.3, respectively, for rats fed high vs. low fat. Additional studies showed that diet had no effect on serum prolactin or estrogen concentrations or metabolism and clearance of intravenously administered radiolabeled prolactin. We demonstrated that high dietary fat concentration enhances breast carcinogenesis independently of cyclic ovarian function, although the presence of estrogen may be a prerequisite for significant dietary modulation. The effect of fat on breast cancer is not mediated by major changes in systemic prolactin metabolism.

Carbopol thickened nanoemulsions of chemotherapeutics to treat DMBA-induced breast cancer

Breast cancer is the most frequent invasive malignancy in women globally. The goal of this study was to prepare mitoxantrone and 4-methyl umbelliferone nanoemulsions followed by hydrogel preparation viz. MTO-NE-Gel and 4-MU-NE-Gel and characterized for various parameters like visual assessment, pH, rheology, ex vivo studies, and in vivo studies in 7,12-dimethylbenz(a)anthracene-induced breast cancer in swiss albino mice. The pH, viscosity, and spreadability were found to be 5.62±0.05, 13107 cP ±658, and 5.3 g.cm/s ±0.28 for 4-MU-NE-Gel and 5.75±0.03, 13025 cP ±705, and 4.06 g.cm/s ±0.45 for MTO-NE-Gel. The percent cumulative amount of drug permeated for 4-MU suspension, MTO Solution,4-MU-NE-Gel, and MTO-NE-Gel were found to be 51.26% ±5.22, 15.54% ±3.91, 89.093% ± 6.8, and 97.242%±4.51 respectively after 8 h which was significantly higher in hydrogel formulations. The outcome of pharmacodynamic studies reveals a significant reduction in tumor weight and tumor volume for MTO-NE-Gel and 4-MU-NE-Gel treated mice as compared to MTO-Gel and 4-MU-sus-Gel. Histopathological evaluation of mammary tumors indicates improvement in the tissue anatomical features and a significant decreasing trend in levels of tumor marker CA15-3 was also observed. Based on the promising results of this investigation,,,

Zingiberene exerts chemopreventive activity against 7,12-dimethylbenz(a)anthracene-induced breast cancer in Sprague-Dawley rats.

Breast cancer is the primary cause of cancer-related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12-dimethylbenz(a)anthracene (DMBA)-stimulated mammary carcinogenesis in rats and MDA-MB-231 cells. Breast cancer was induced in the Female Sprague-Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor-α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA-MB-231 cells. Zingiberene substantially modulated the DMBA-stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA-stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA-MB-231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA-stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent.

Extra-Virgin Olive Oil and Its Minor Compounds Influence Apoptosis in Experimental Mammary Tumors and Human Breast Cancer Cell Lines.

Simple SummaryBreast cancer is a disease influenced by dietetic factors, such as the type and amount of lipids in a diet. In this work, we aimed to elucidate the different effects of two high-fat diets on the histopathological and molecular characteristics of mammary tumors in an experimental model. Animals fed with a diet high in extra-virgin olive oil (EVOO), compared to those fed with a diet high in seed oil, developed tumors with less aggressiveness and proliferation. Tumor molecular analyses of several cell death pathways also suggested an effect of EVOO in this process. In vitro experiments indicated the role of EVOO minor compounds on the effects of this oil. Obtaining insights into the influence and the mechanisms of action of dietary compounds are necessary to understand the relevance that dietetic habits from childhood may have on health and the risk of disease.Breast cancer is the most common malignancy among women worldwide. Modifiable factors such as nutrition have a role in its etiology. In experimental tumors, we have observed the differential influence of high-fat diets in metabolic pathways, suggesting a different balance in proliferation/apoptosis. In this work, we analyzed the effects of a diet high in n-6 polyunsaturated fatty acids (PUFA) and a diet high in extra-virgin olive oil (EVOO) on the histopathological features and different cell death pathways in the dimethylbenz(a)anthracene-induced breast cancer model. The diet high in n-6 PUFA had a stimulating effect on the morphological aggressiveness of tumors and their proliferation, while no significant differences were found in groups fed the EVOO-enriched diet in comparison to a low-fat control group. The high-EVOO diet induced modifications in proteins involved in several cell death pathways. In vitro analysis in different human breast cancer cell lines showed an effect of EVOO minor compounds (especially hydroxytyrosol), but not of fatty acids, decreasing viability while increasing apoptosis. The results suggest an effect of dietary lipids on tumor molecular contexts that result in the modulation of different pathways, highlighting the importance of apoptosis in the interplay of survival processes and how dietary habits may have an impact on breast cancer risk.

Effect of Preventive Acupunture Combined with CMNS6-1 Electroacupuncture Instrument on Promoting Apoptosis of 7,12-Dimethylbenzene (a) Anthracene-Induced Breast Cancer Model Rats

The purpose of this study was to evaluate the effect of preventive acupuncture combined with CMNS6-1 electroacupuncture on 7,12-dimethylbenzanthracene induced mammary tumors in Sprague-Dawley rats and to explore the effect of preventive acupuncture on mammary tumors from the perspective of apoptosis. 48 w old female Sprague-Dawley rats were randomly divided into control (10), model (10), tamoxifen (10) and preventive acupuncture (10) groups. The model group, tamoxifen group and preventive acupuncture group were administered once intragastrically with 100 mg/kg body weight of 7,12-dimethylbenzanthracene to induce spontaneous breast cancer. On d 1 after modeling, acupuncture plus electrical stimulation was administered to the preventive acupuncture group. Density wave was selected for electrical stimulation with a frequency of 2 Hz/100 Hz and an intensity of 1 mA and three acupoints, "Zu San Li", "San Yin Jiao" and "Tan Zhong", were stimulated for 20 min per treatment, once every other day, three times a week for 16 w. Tamoxifen (3 mg/kg body weight, intragastrically, every day) was started the day after 7,12-dimethylbenzanthracene administration and continued for 16 w, as positive control treatment. Apoptosis of breast tumor tissue cells was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and expression of caspase-3 and B-cell lymphoma-2 was assessed by immunohistochemistry. During the experiment, no tumors were detected in rats from the control+sham group, all the rats in the 7,12-dimethylbenzanthracene+sham group developed tumors and the cumulative incidence of tumors was 100 %, meanwhile the cumulative incidence of tumors in the 7,12-dimethylbenzanthracene+preventive acupuncture group and the 7,12-dimethylbenzanthracene+tamox group were 60 % and 50 %, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assay showed that preventive acupuncture could significantly promote apoptosis in breast tumor cells in 7,12-dimethylbenzanthracene induced rat, while increased the expression levels of pro-apoptotic proteins such as caspase-3 and B-cell lymphoma-2 associated X. The expression level of antiapoptotic protein B-cell lymphoma-2 was down-regulated and the ratio of B-cell lymphoma-2/B-cell lymphoma-2 associated X was increased. Preventive acupuncture therapy combined with CMNS6-1 electroacupuncture instrument inhibited 7,12-dimethylbenzanthracene-induced mammary tumorigenesis in rats and the mechanism may be related to the regulation of apoptosis-related protein expression and promotion of tumor cell apoptosis.

Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer.

Breast cancer is the most common estrogen-dependent cancer in the world. Hormone therapy for this cancer can be neoadjuvant and/or adjuvant. Herbal remedies with antiproliferative properties are believed to be potential anticancer agents. The aqueous extract of Dacryodes edulis (Burseraceae) leaves (AE), a medicinal plant used against cancer in Cameroon, was found to display antiproliferative effects in ovariectomized rats. Compounds isolated from this plant exhibited anticancer activity in vitro. To determine whether AE has an anticancer potential, its effects were investigated in rats with already developed breast cancer. Mammary tumors were induced by a single subcutaneous administration (under the mammary gland) of 7,12-dimethylbenz[a]anthracene (DMBA; 50 mg/kgBW) to immature female rats. After 22–26 weeks of observation, animals with palpable tumors were treated with tamoxifen (3.3 mg/kgBW) and AE at doses of 25 and 100 mg/kgBW. The negative control received distilled water. Treatments were given orally for 21 consecutive days. The volume of mammary tumors was evaluated weekly using a caliper. On day 22, animals were sacrificed. Cholesterol and estradiol levels were assessed in serum, breast tumors, mammary glands, and ovaries. Oxidative status of tumors was evaluated. The histological analysis of mammary glands and breast tumors was performed. Results showed that AE reduced tumor volume and weight (p < 0.05). This effect was associated with reduced cholesterol (p < 0.001) and estradiol (p < 0.01) levels in breast tumors, serum, ovaries, and mammary glands. AE also increased tumors levels of malondialdehyde (p < 0.05) and antioxidant enzymes (p < 0.01). These effects contributed to the decrease in the size of breast alveoli (p < 0.01), the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the aqueous extract of D. edulis leaves, thanks to its ability to inhibit tumor growth, could be considered as a potential alternative for the neoadjuvant treatment of estrogen-dependent breast cancer.

Histopathological evaluation of Senecio rhizomatus Rusby in 7,12-dimethylbenz(α) anthracene-induced breast cancer in female rats.

Background and Aim:Senecio rhizomatus Rusby (SrR) is a medicinal plant of the Asteraceae family and traditionally consumed as infusion in the Andean region from Peru for inflammatory disorders. This study aimed to determine the histopathological changes afforded by SrR in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer (BC) in rats.Materials and Methods:An ethanolic extract of SrR aerial parts was prepared by maceration with 96% ethanol, and the chemical components were identified by gas chromatography coupled to mass spectrometry; the antioxidant activity was determined by 1,1-diphenyl-2-picril-hidrazil (DPPH) assay; and the acute toxicity was assessed according to the OCED 423 guidelines. In a pharmacological study, 30 female Holztman rats were distributed randomly into five groups, as follows. Group I: Negative control (physiological serum, 2 mL/kg); Group II. DMBA (80 mg/Kg body weight); and Groups III, IV, and V: DMBA + ethanol extract of SrR at doses of 10, 100, and 200 mg/kg, respectively.Results:The antioxidant activity of the SrR extract against DPPH was 92.50% at 200 mg/mL. The oral administration of SrR at doses of 50, 300, 2000, and 5000 mg/kg did not show any clinical evidence of toxicity or occurrence of death. The groups that received SrR presented a lower frequency of tumors and acumulative tumor volume compared with the DMBA group (p<0.05); the DMBA group exhibited a higher incidence of necrosis and moderate mitosis, up to 66.67% and 100.00%, respectively. Finally, infiltrating carcinoma with extensive tumor necrosis was evidenced.Conclusion:In experimental conditions, the ethanolic extract of SrR had a protective effect in DMBA-induced BC in female rats. Furthermore, the antioxidant activity of its main phytochemicals could be responsible for the effect observed, and SrR seems to be a safe extract in the preclinical phase.

Chemopreventive effect of tomentosin against 7,12-dimethylbenz[a] anthracene-induced breast cancer progression and inhibits the cell proliferation in MCF-7 cells via downregulation of PI3K/AKT signaling pathway

Background: Breast cancer is the most common cancer which disturbs not only the older population but also women under 35 years old. It also ranks to be the first in cancer-connected deaths of women. Objectives: Hence, we intended the study to investigate the efficacy of tomentosin as an anticancer agent against breast cancer in vitro and in vivo conditions. Materials and Methods: Breast cancer was persuaded to the rats by DMBA administration and then treated with the tomentosin for 28 days. The levels of estrogen receptor α (ER-α), oxidative stress markers, biotransformation enzymes, carcinoembryonic antigen, and cytokines were assessed. Histopathological analysis was done to check the anticancer effect of tomentosin. In vitro studies were finished with MCF-7 cells and the cells were exposed to cell viability assay and different fluorescent staining assays such as H2DCFDA, JC-1, and AO/EtBr dual staining to inspect the tomentosin effects. The expression of PI3K/AKT signaling molecules was considered by quantitative polymerase chain reaction (qPCR) analysis. Results: Our in vivo consequences recommend tomentosin knowingly reduced the levels of ER-α, CYP450, CYT-b5, carcinoembryonic antigen, and cytokines and augmented the levels of CAT, GST, and GR enzymes. Histological results authorize anticancer effects of tomentosin. The qPCR results exhibited that tomentosin significantly lessened the expression of PI3K/AKT and augmented the apoptosis-related p38/JNK1 expression in MCF-7 cells. Conclusion: Overall, our results settle tomentosin possibly inhibit the DMBA-convinced breast cancer induction in rats and they also induce apoptosis in estrogen-dependent breast cancer MCF-7 cell lines.

Cytotoxic and cancer chemopreventive potentials of the Anthonotha macrophylla P. Beauv aqueous extract on 7,12-dimethylbenz[a]anthracene-induced breast cancer in rats

Breast cancer is one of the leading causes of cancer deaths in women worldwide. Many women rely on plants as alternatives to prevent/treat cancer. Anthonotha macrophylla (Ceasalpiniaceae) is one of this ethnomedicinal plant used to cure cancer in Cameroon. This study was therefore undertaken to bring scientific evidence to this claim. The in vitro cytotoxicity of A. macrophylla aqueous extract was evaluated using resazurin reduction assay in five tumors and two non-tumor cell lines. Moreover, the chemopreventive potential of A. macrophylla aqueous extract was evaluated on 7,12 dimethylbenz[a]anthracene (DMBA) induced breast cancer in rats. The research focused on the incidence, burden, volume and histological analysis of breast tumors. In vitro, A. macrophylla extract exhibited cytotoxic effect in all tested cell lines with a CC50 ~ 279 and 132 μg/mL in human (MCF-7 and MDA-MB-231) and rodent breast cancer cells, respectively after 24 h. In vivo, the untreated DMBA-rats presented 100% of tumor incidence, while no tumor was detected in normal rats. Interestingly, a seven-month oral administration of A. macrophylla extract at the doses of 75 and 150 mg/kg BW resulted in a significant decrease of tumor incidence (p < 0.01 and p < 0.05), burden (70.01% and 53.28%) and volume (p < 0.001 and p < 0.01) compared to DMBA rats. The presence of polyphenols in the aqueous extract of Anthonotha macrophylla, as well as its antiradical properties, may account for its antitumor effects. These results therefore support the traditional use of Anthonotha macrophylla against breast cancer.

Study of anticancer activity of cecropin B on 7, 12-dimethylbenz (a) anthracene-induced breast cancer

Background and aims: Antimicrobial peptides constitute a family of bioactive peptides that are involved in the body defense. Recently, their anti-cancer properties, especially by inducing apoptosis, have been proven in in vitro studies. Therefore, in this study, the effects of cecropin B as an antimicrobial peptide on breast cancer growth, hematological parameters, and histopathological changes in rats were evaluated. Methods: Twenty-four female rats were randomly divided into 4 groups. The cancer group, control group, cecropin B group, and cancer group treated with cecropin B. The tumor size was measured at the beginning and the completion of the treatment period. Blood samples were collected for assessment of the hematological parameters and Bax and Bcl2 levels. Tumor tissues were removed for histopathological analysis. Results: The tumor size had a significant increase in the cancer group and cancer group treated with cecropin at the end of the treatment. A significant decrease in mean cell volume, white blood cell count and Bcl2 level and a significant increase in hemoglobin and Bax levels were observed in the cancer group treated with cecropin B compared to cancer group. Changes in other parameters were not significant. Histopathological study showed the invasion of mitotic cells to stromal and muscular tissues of the breast in the cancer group, while focal destruction of tissue and cell death were observed in the cancer group treated with cecropin B. Conclusion: The results showed that cecropin B has been able to reduce tumor growth and have little side effects on hematologic factors probably through apoptosis.

Tumor suppressive effect of Artemisia annua extract in 7, 12-dimethylbenz[a]anthracene-induced breast cancer in Wistar rats

Tumor suppressive effect of Artemisia annua extract in 7, 12-dimethylbenz[a]anthracene-induced breast cancer in Wistar rats

Modulatory Effects of Concanavalin A and D 609 on Apoptotic Markers in Dimethylbenz (a) anthracene induced Breast Cancer in Rats

The present study was conducted to evaluate the chemopreventive efficacy and modulatory effects of concanavalin A and D609; either individually or in combination, on some apoptotic markers in Dimethylbenz (a) anthracene (DBMA) induced breast cancer in rats. Breast cancer was induced in adult female albino rats by injection of DMBA (50 mg/kg b. wt.). After 15 weeks, animals and divided into four groups. One group did not receive any treatment and served as a tumor group. The other three groups were injected with concanavalin A (of 20 mg/kg b. wt.) or D609 (50 mg / kg b. wt.) or both components together for a period of 8 weeks. At the end of experimental period, animals of control and treated groups were sacrificed and samples of breast tissues were obtained and prepared for analysis of the apoptotic markers Bcl-2 (B -cell leukemia/ lymphoma 2), Bim (BcL2 interacting mediator), Bax (Bcl-2 associated X protein), Caspase 9, and Caspase 3. The results exhibited highly significant changes in apoptotic markers in cancer group as compared to normal control group, mainly represented by the increased levels of Bcl-2 and decreased levels of Bim, Bax and caspases 3 and 9. On the other hand, concanavalin A and D609 treatments induced significant modulatory effects on these markers. They induced significant decrease in Bcl-2 levels and increase in Bim, Bax and caspases 3 and 9 levels in all treated groups as compared to the DBMA-tumor group. These ameliorative changes were highly significant in the group of animals exposed to co-treatment of both materials. To conclude: the present study provides evidence that concanavalin A and D609 enhance apoptotic activity in DMBA-induced breast cancer in rats and suggests that the use of combination of the two therapies is recommended in the treatment of breast cancer.

The potential therapeutic effect of NG-hydroxy-nor-L-arginine in 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

Advances in our understanding of the metabolism and molecular functions of arginine and their alterations in cancer have led to resurgence in the interest of targeting arginine catabolism as an anticancer strategy. Therefore, arginase inhibitors have been proposed as a way to treat cancer. In this study, the anti-tumor potential of the arginase inhibition by NG-hydroxy-nor-L-arginine (nor-NOHA) (3 mg/kg/day, i.p.), administered for 5 weeks (parallel tumors development, every 3th day) against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in rats has been investigated. Treatment by nor-NOHA has obvious inhibition effects on development of carcinogenesis in rats was shown. That was seen in downregulation of rats' tumors size and number, mortality rate, in stopped alteration of tissue histopathology, in decrease of polyamines, NO and MDA (malondialdeide) concentrations (in blood). Results have shown arginase and NO-synthase can cooperate to restrain quantities of polyamines and NO for cancer progression. The results obtained can serve as a base to use this model for determination of productive, noncytotoxic antitumor and immune modulating concentration of anticancer agents. Perspectives of targeting arginase and NOS in cancer management can ground application in clinical medicine.

Effects of the Cell Debris and Supernatant of Saccharomyces boulardii on 7,12-Dimethylbenz(a) Anthracene-Induced Breast Cancer in Rats

Background: Saccharomyces boulardii is a probiotic yeast with a demonstrated ability to inhibit different cancer cell lines. Objectives: The present study was conducted to evaluate the protective effects of the cell debris and supernatant of Saccharomyces boulardii on breast cancer induced by 7,12-Dimethylbenz(a) anthracene (DMBA) in rats. Methods: After culturing Saccharomyces boulardii on dextrose agar, the cell debris and supernatant were collected. The present study was conducted on 32 rats weighing 150 ± 20 g in four groups, including the injection control group, the cancer group, the group treated with the cell debris of Saccharomyces boulardii and the group treated with the supernatant. Hematological factors were evaluated after the treatment. Histopathological changes and concentrations of BAX and Bcl-2 were also assessed in the tumors. Results: Significant changes were observed in all the blood factors in the cancer compared to control group, whereas no significant changes were observed in the two groups treated with the supernatant and cell debris of Saccharomyces boulardii compared to in the control group except for a significant increase in MCV. Deformed mammary acini and an increased volume of milk glands confirmed the duct carcinoma. Although fewer pathological carcinogenic changes were observed in the two groups treated with the supernatant and cell debris of Saccharomyces boulardii, the appearance of the tissues was still inflamed. The concentration of BAX significantly increased and that of BCL-2 significantly decreased in the group treated with the Saccharomyces boulardii supernatant compared to in the cancer group. Conclusions: Saccharomyces boulardii and its supernatant could reduce the size of the tumor and inhibited its spread to other parts of the body by inducing apoptosis in the tumor cells.

Discovery of Glabridin as Potent Inhibitor of Epidermal Growth Factor Receptor in SK-BR-3 Cell

The breast cancer is the leading cause of death in women. Therefore, objective of the present study was to examine the antibreast cancer effect of glabridin (GBN) and to evaluate its mechanism of action. In this study, we have demonstrated that GBN causes reduction of cellular viability of human breast cancer SK-BR-3 in MTT assay. Results from Hoechst 33342 and propidium iodide staining assay suggested that GBN causes significant enhancement in the apoptosis. At the molecular level, in western blot analysis, GBN causes significant increase in c-PARP and c-caspases 3, 8, and 9 concentrations in a dose-dependent manner in breast cancer cells. The GBN further showed reduced level of p-epidermal growth factor receptor, p-AKT, p-ERK1/2, and cyclin D1 as the concentration rose in treated cells. Subsequent to this, GBN showed beneficial effect in 7,12-dimethylbenz[a]anthracene-induced breast cancer in experimental mice as confirmed by increase in body weight, reduction in tumor volume, oxidative stress, and dose-dependent restoration of all tested enzymes (phase I and II) in the treated group. GBN may, thus, play a protective role as an antibreast cancer drug for the prevention of breast cancer.

Potential of Regular Consumption of Cameroonian Neem (Azadirachta indica L.) Oil for Prevention of the 7,12-Dimethylbenz(a)anthracene-Induced Breast Cancer in High-Fat/Sucrose-Fed Wistar Rats.

Neem (Azadirachta indica) is a tree from the Meliaceae family native to India, where it is considered as one of the most important plants worldwide. The anticancer effects of neem oil on breast cancer cells have been recently reported; however, its in vivo effects have not been studied. This prompted us to investigate the protective effects of neem oil on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in high-fat/sucrose-fed Wistar rats. Juvenile female Wistar rats were treated either with neem oil at a dose of 3 mL/kg body weight at 3 different frequencies, 2 times/week (Neem 1), 4 times/week (Neem 2), and every day (Neem 3), or with tamoxifen (3.3 mg/kg body weight), starting 1 week prior to DMBA treatment and lasting 12 weeks. Incidence, burden, volume, and histological analysis of mammary tumors were measured. Further toxicological parameters have been assessed. No tumors were detected in rats from the normal group, while all the rats from the negative control group (100%) developed mammary tumors. The regular consumption of neem oil at a dose of 3 mL/kg (2 or 4 times/week) significantly (p < 0.01) and in a dose-dependent manner reduced tumor incidence (80%), burden [35.78% (2 times/week) and 36.09% (4 times/week)], and weight. Neem consumption protected rats against DMBA-induced breast hyperplasia, with an optimal effect when taken 4 times weekly. Interestingly, all the animals that received a daily dose of 3 mL/kg died at the third week of the experiment. Further, animals that took the neem oil 4 times per week developed hepatotoxicity, evidenced by an increase of liver wet weight, transaminase (ALT and AST) activity, and histological abnormalities in liver. This study brings insight into the use of neem oil, which is greatly appreciated in traditional medicine. In summary, we demonstrated for the first time that the regular consumption of neem oil prevents breast cancer, but its excessive consumption is toxic.