Cancer In Female Rats Research Articles

Comparative anticancer effects of Annona muricata Linn (Annonaceae) leaves and fruits on DMBA-induced breast cancer in female rats

BackgroundNumerous studies have reported the anti-cancer effects of different parts of Annona muricata Linn, however ; most of them focused on the in vitro evaluation of isolates. In vivo evidence on which part is best suited for breast cancer chemoprevention remains to be demonstrated. This is a comparative study of the effects of A. muricata fruit and leaves extracts on DMBA induced-breast cancer in rats.MethodsRats exposed to DMBA (50 mg/kg, s.c.), were treated with A. muricata fruit aqueous extract at 200 mg/kg BW (3 days/week or daily) and A. muricata Linn leaves ethanolic extract at 200 mg/kg daily. Positive control group received tamoxifen at 3.3 mg/kg, while the normal and diseased controls received vehicle. After 20 weeks of treatment, the tumor incidence, tumor burden, tumor volume, histopathology, protein and CA 15 − 3 levels as well as antioxidant status, pro-inflammatory cytokines were assessed.ResultsThus, 100% of diseased rats presented cribriform ductal carcinoma of SBR grade III. A. muricata extracts (leaves and fruit) and tamoxifen significantly reduced death and tumor incidences, volume and weight of the tumors, total protein and CA15-3 levels compared to the DMBA group. They exhibited antioxidant activity, through an increase in the GSH level and SOD and catalase activities with reduced levels of MDA compared to DMBA group. TNF-α, IL-6 and INF-γ levels reduced with regards to A. muricata treatment.ConclusionThese results confirm the anti-breast cancer effect of A. muricata, however, the aqueous fruit extract was more potent than the ethanolic leaves extract.

ANTI-CANCER ACTIVITY OF GRAVIOLA (ANNONA MURICATA) LEAVES EXTRACT ON INDUCED BREAST CANCER IN RATS’ MODEL

Breast cancer is the most frequent type of invasive cancer in women. However, chemotherapy affects all cells that grow and divide quickly in the body, including cancer and normal cells. On the other hand, Graviola is commonly used as a source of food and has a wide range of bioactive components. In this study, out of 50 albino rats, breast cancer was induced in 40 rats using 7,12-dimethylbenanthracene (DMBA). These rats were subjected to the treatment using Graviola leaves ethanolic extract (GLEE) and 5-Fluorouracil (5-FU) to evaluate the anti-carcinogenic activity and the immunohistochemical changes. A single oral dose of DMBA led to the induction of rats’ breast cancer. Induced mammary tumors were diagnosed, and all were malignant without any benign tumor. Among the malignant tumors, non-invasive, invasive, mixed (invasive and non-invasive), and unclassified malignant tumors were detected. The immunohistochemical analysis showed that estrogen and progesterone receptors revealed negative nuclear expression. However, HER2 receptors score was +3, and Ki-67 revealed 85-90% nuclear stainability, denoting a very high proliferative index. The morphometric analysis revealed that staining reactivities of HER2 and Ki-67 were 60.66 and 89.84%, respectively, and were significantly higher than ER (15.24 %) and PR (15.68%). Genetic studies revealed marked upregulation of P53 with GLEE more than 5-FU while Bcl2 showed down regulation with GLEE more than 5-FU. The quantitative analysis of GLEE phytochemical constituents showed the presence of some bioactive chemical compounds that exhibit many therapeutic activities. Therefore, GLEE improved histological appearance of DMBA induced breast cancer in female rats. Therefore, GLEE could be a promising natural alternative to chemotherapy agents as a potent anticancer.

Protective effects of hesperidin through attenuation of Ki67 expression against DMBA-induced breast cancer in female rats

AimsDoxorubicin (Dox) is routinely used for breast cancer treatment but toxicity and drug resistance limit its use. The objective of the study was to investigate the protective effects of hesperidin alone and in combination with doxorubicin against experimentally induced breast cancer in female rats. MethodsBreast cancer (BC) was induced by administration of 7,12-dimethylbenz(a)anthracene (DMBA) through subcutaneous injection into the 3rd right mammary gland of female Wistar rats. Hesperidin (Hes) pretreated groups were started with Hes (200 mg/kg) two weeks prior to DMBA induction. Animals were randomly divided into nine groups namely vehicle control, DMBA-induced, Dox 4 mg/kg, Dox 2 mg/kg, Hes (200 mg/kg), Hes (200 mg/kg) plus Dox 4 mg/kg treated groups and Hes pretreated groups treated with DMBA, Dox 4 mg/kg and Dox 2 mg/kg. Key findingsHes pretreated groups showed reduced tumor occurrence, tumor volume and increased survival rate as compared to DMBA-induced group of animals. Hes pretreated animals treated with Dox 4 mg/kg and 2 mg/kg exhibited significant reduction in malondialdehyde and improvement in levels of glutathione and inflammatory markers like IL-6, TNF-α, NF-κB, IFN-γ as compared to Dox 4 mg/kg and 2 mg/kg treated animals. Histopathology and Ki67 expression depicted better control of tumor with Hes pretreatment groups as compared to DMBA-induced. Histopathology of vital organs of Hes pretreated groups treated with Dox revealed lesser toxicity than Dox treated groups. SignificanceHesperidin possesses protective effect against experimentally induced breast cancer in female rats that appears to be related to attenuation of Ki67 expression.

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.

The Essential Oil of Cymbopogon citratus Stapt and Carvacrol: An Approach of the Antitumor Effect on 7,12-Dimethylbenz-[α]-anthracene (DMBA)-Induced Breast Cancer in Female Rats.

C. citratus essential oil and carvacrol have shown an antitumor effect on breast tumor cell lines; the main objective of this research was to evaluate the antitumor effect of the essential oil of Cymbopogon citratus (EOCc) and carvacrol on 7,12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in female rats. Cancer was induced by a single administration of DMBA at dose of 80 mg/kg body weight (BW). A total of 54 female Holtzman rats were randomly assigned into 9 groups (n = 6). Group I: PS (Physiological saline); Group II: DMBA; Groups III, IV, and V: DMBA + EOCc at doses of 50, 100 and 200 mg/kg/day BW, respectively; Groups VI, VII, and VIII: DMBA + carvacrol at doses of 50, 100 and 200 mg/kg/day BW, respectively; and group IX: DMBA + EOCc + carvacrol at doses of 100 mg/kg/day BW. The treatment lasted 14 weeks. As results, EOCc showed a reduction in tumors as well as necrosis and mitosis. Animals treated with carvacrol did not show necrosis, mitosis, or infiltration. Carvacrol at dose of 100 mg/kg/day BW revealed a significant decrease in the cumulative tumor volume down to 0.11 ± 0.05 cm3 compared to 0.38 ± 0.04 cm3 of the DMBA group (p < 0.01). It is concluded that EOCc and carvacrol had an antitumor effect on DMBA-induced breast cancer in female rats.

The Effect of Zinc and Melatonin Administration on Lipid Peroxidation, IL-6 Levels, and Element Metabolism in DMBA-Induced Breast Cancer in Rats

The purpose of this study was to investigate the effects of zinc and melatonin administration on interleukin-6, lipid peroxidation parameters, and element metabolism in DMBA-induced breast cancer in female rats. A total of 42 recently weaned Wistar rats were divided into 5 groups as follows: control (group 1), DMBA control (group 2), DMBA + zinc (group 3), DMBA + melatonin (group 4), and DMBA + melatonin and zinc (group 5). Malondialdehyde (MDA) and glutathione (GSH) levels in breast tissue and blood samples were determined via spectrophotometric methods. In addition, iron, magnesium, zinc, and copper levels in serum samples were determined by atomic emission, and plasma interleukin-6 levels were determined by ELISA method. The highest tissue and plasma MDA and the lowest tissue and erythrocyte GSH levels found in the study were in group 2; the highest tissue and erythrocyte GSH levels and the lowest tissue and plasma MDA levels are in group 5 (P < 0.05). Iron, magnesium, and zinc levels of groups 3, 4, and 5 were higher than the DMBA group without administration (group 2), but the copper values were significantly lower (P < 0.05). The highest IL-6 levels were determined in group 2 while IL-6 levels in the DMBA group (G5) treated with combined melatonin and zinc were lower than all other breast cancer groups (P < 0.05). According to the findings obtained in this presented study, combined zinc and melatonin therapy can contribute to the prevention of tumor growth by improving the disruption in element metabolism and suppressing IL-6 levels and reducing tissue damage that causes the cancer.

The Effect of Zinc and Melatonin Supplementation on Lipid Peroxidation of Various Tissues of Rats with by DMBA-Induced Breast Cancer

The purpose of this study was to investigate the effects of zinc and melatonin administration on lipid peroxidation in various tissues in DMBA-induced breast cancer in female rats. A total of 42 recently weaned Wistar rats were divided into 5 groups in the study: Group 1 (Control), Group 2 (DMBA Control), Group 3 (DMBA+Zinc), Group 4 (DMBA+Melatonin), Group 5 (DMBA+Melatonin, and Zinc). MDA (malondialdehyde) and GSH (glutathione) levels were determined via the spectrophotometric method in the lung, liver, spleen, pancreas, and kidney tissue samples taken from experimental animals. The highest lung, liver, spleen, pancreas, and kidney tissue MDA levels were obtained in the DMBA-induced breast cancer group control group (G2) (p&lt;0.05). MDA levels in DMBA+Zinc (G3), DMBA+Melatonin (G4), and DMBA+Melatonin and Zinc (G5) were significantly lower than group 2 (p&lt;0.05). Similarly, lung, liver, spleen, pancreas, and kidney tissue GSH levels of DMBA+Zinc (G3), DMBA+Melatonin (G4), and DMBA+Melatonin and Zinc (G5) were significantly higher than that of Group 2 (p&lt;0.05). The findings of the study indicated that increased lung, liver, spleen, pancreas, and kidney damage in DMBA-induced breast cancer is suppressed with the supplementation of zinc, melatonin, and combined zinc and melatonin.

Zinc and melatonin supplementation ameliorates brain cortex tissue damage in DMBA-induced breast cancer in rats.

This study aims to investigate the effects of zinc and melatonin supplementation on lipid peroxidation in the brain cortex in DMBA-induced breast cancer in female rats. A total of 42 recently weaned Wistar rats were divided into 5 groups as follows: Control (Group 1), DMBA Control (Group 2), DMBA+Zinc (Group 3), DMBA+Melatonin (Group 4), DMBA+Melatonin et Zinc (Group 5). At the end of the study, all animals were sacrificed by decapitation and Malondialdehyde (MDA) and glutathione (GSH) levels in brain cortex tissue samples were determined via spectrophotometric methods. The highest MDA levels were in the DMBA-treated group (Group 2) (p<0.05). MDA levels in Group 3, Group 4, and Group 5 were significantly lower than in group 2 (p<0.05). Also, GSH levels in group 3, 4, and 5 were significantly higher than in group 2 (p<0.05). There are no reports on whether DMBA-induced experimental breast cancer affects oxidative stress in brain tissue. In this respect, our study revealed that the increased brain cortex tissue damage in DMBA-induced breast cancer is alleviated by Zinc, melatonin, or combined zinc and melatonin treatment (Fig. 3, Ref. 26).

Carvacrol: An In Silico Approach of a Candidate Drug on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR Receptors in the Breast Cancer.

Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[α]anthracene- (DMBA-) induced breast cancer in female rats. The main objective in this research was to evaluate by using in silico study the carvacrol on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR receptors involved in breast cancer progression by docking analysis, molecular dynamic, and drug-likeness evaluation. A multilevel computational study to evaluate the antitumor potential of carvacrol focusing on the main targets involved in the breast cancer was carried out. The in silico study starts with protein-ligand docking of carvacrol followed by ligand pathway calculations, molecular dynamic simulations, and molecular mechanics energies combined with the Poisson–Boltzmann (MM/PBSA) calculation of the free energy of binding for carvacrol. As result, the in silico study led to the identification of carvacrol with strong binding affinity on mTOR receptor. Additionally, in silico drug-likeness index for carvacrol showed a good predicted therapeutic profile of druggability. Our findings suggest that mTOR signaling pathway could be responsible for its preventive effect in the breast cancer.

Naringenin inhibits migration of breast cancer cells via inflammatory and apoptosis cell signaling pathways.

Naringenin, a flavonoid compound, has a wide variety of uses in the pharmaceutical industry for its antioxidant and anti-inflammatory potential. The current experiment aimed to investigate the anticancer effect of naringenin in triple-negative human breast cancer cells (MDA-MR-231) and an animal model with 7,12-dimethylbenz[a] anthracene (DMBA)-induced breast cancer in female rats to determine the mechanisms and molecular targets. The cytotoxic effects of naringenin against MDA-MB-231 cells were assessed by MTT assay. Apoptosis and cell cycle alterations were analyzed via flow cytometry. Morphological and biochemical changes in DMBA-induced cancer with naringenin treatment were assayed using our protocol. The potential mechanisms of action were verified via qRT-PCR. Naringenin was found to inhibit cell proliferation in a time- and concentration-dependent manner. This effect was associated with cell cycle arrest at the G0/G1 phase, along with apoptosis and deposition at the sub-G1 phase (75%). Treatment with naringenin reduced tumor incidence (45.55, 40, and 27.67%) and tumor burden (78.7, 35.4, and 1.2g) in a dose-dependent manner. Naringenin treatment altered the biochemical and antioxidant parameters related to inflammation necessary for anticancer activity. The qRT-PCR studies further confirmed the mitochondrial-mediated apoptotic effects of naringenin. On the basis of these results, we can conclude that naringenin exerts an anticancer effect in the MDA-MB-231 cell line that arrests cell development at the G0/G1 phase, and in vivo it alters the mitochondrial-mediated intrinsic pathway responsible for apoptosis.

Effects of Enoxaparin Emulsion on Dimethylbenzanthracene-induced Breast Cancer in Female Rats

Introduction: Enoxaparin is an anticoagulant medication. Anticoagulation inhibits tumor cell-mediated release of angiogenic proteins and diminishes angiogenic response. Angiogenesis is an important event in various cancers such as breast cancer. Angiogenesis provide oxygen and nutrients to tumor cells and causes tumor progression. The aim of the present study was to evaluate the anti-angiogenesis effect of an enoxaparin cream on breast cancer induced by dimethylbenzanthracene in rats. Methods: In this experimental in vivo study, 50 Wistar female rats were divided into negative control (vehicle), positive control (cream base), and 3 groups with enoxaparin treatment (40, 60, and 80 mg/ml). After one month of treatment along with breast cancer induction by dimethylbenzanthracene, breast tissue samples were isolated and stained with hematoxylin-eosin, and tumor growth suppression rate was calculated. Tumor size (length and width) was measured using a clipper, and the tumor volume was calculated using the following formula: V = (L × W × W)/2, where V is tumor volume, W is tumor width, L is tumor length. The data were analyzed using one-way ANOVA and Tukey’s post hoc test. Results: Tumor suppression was significantly increased in enoxaparin treatment groups compared to the positive control group (40 mg/ml of enoxaparin treated versus positive control group; P = 0.017, 60 mg/ml of enoxaparin treated versus positive control; P = 0.015, 40 mg/ml of enoxaparin treated versus positive control; P = 0.009, 60 mg/ml of enoxaparin treated versus 40 mg/ml of enoxaparin treated; P = 0.019, and 80 mg/ml of enoxaparin treated versus 40 mg/ml of enoxaparin treated; P = 0.011 in a dose-dependent manner. Conclusion: Enoxaparin inhibits breast cancer in a dose-dependent manner. The application of enoxaparin cream in patients with breast cancer may considerably reduce tumor growth.

Antitumor Effect of Mesenchymal Stem Cells from Murine in Breast Cancer in Female Rats

The aim of this study was to evaluate the effect of mesenchymal stem cells as a treatment against breast cancer via modulation TGF-β. Mesenchymal stem cells (MSCs) are recruited to the stroma of cancers. They interact with cancer cells to promote invasion and metastasis or to suppress tumor growth. The unique tumor-homing capacity of MSCs makes them a promising vehicle to deliver various anticancer agents.

Effect of Nanoselenium on Experimentally Induced Mammary Cancer in female Rats: Possible Role of TGF-β1

Effect of Nanoselenium on Experimentally Induced Mammary Cancer in female Rats: Possible Role of TGF-β1

Antitumor Activities of the Novel Isosteviol Derivative 10C Against Liver Cancer.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fifth most common primary malignancy with worldwide increasing incidence. The current study aimed to investigate the anticancer activities of novel isosteviol derivatives towards human HepG2 hepatocellular cancer cells and in an animal model of hepatocellular carcinoma. Twelve isosteviol derivatives were screened for their anti-proliferative activities against HepG2 and IC50 was calculated for all designed derivatives. The impact of the potent isosteviol derivative 10C on HepG2 cells was further studied by MTT assay, Annexin V/PI staining, flow cytometry and western blotting. In vivo studies were performed to assess the anticancer effect of isosteviol derivative 10C on Diethyl Nitrosamine-induced liver cancer in female rats by evaluating the physiological processes. isosteviol derivative 10C induced growth inhibition with IC50 of 2 μM mainly through induction of apoptosis in HepG2 cells. Additionally, isosteviol derivative 10C induced G1 phase arrest, which was further confirmed by increased expression of cyclin dependent kinase inhibitor 1A (CDKN1A, p21). It also increased BAX, BID and PARP-1 and while it reduced pro-CASPASE-3 expression and phosphorylation levels of AKT in HepG2 cells. Furthermore, western blotting data showed that E-cadherin, β-catenin, VEGF and COX-2 expressions were suppressed by isosteviol derivative 10C in HepG2 cells. The in vivo study demonstrated that dose-dependent treatment of isosteviol derivative 10C led to significant reduction in tumor size compared to the untreated group after the fourth injection with no significant effects on major physiological processes. Taken together, in vitro and in vivo studies revealed that isosteviol derivative 10C induced apoptosis in HepG2 cells, blocked angiogenic signaling and it did not induce any apparent toxicity towards the treated hosts which merits further investigation at clinical level.

Protection Against Dimethylbenz[a] Anthracene-Induced Breast Cancer in Female Rats by α-Lactalbumin.

Consumption of α-lactalbumin as dietary protein offers a beneficial effect on breast cancer development. Breast cancer was developed by gavage administration of single dose of dimethylbenz(a)anthracene (DMBA) in female rats, maintained on AIN-76A diet with either 20% casein or α-lactalbumin (a component of whey protein). All tumors were detected by palpation. After approximately 130 days of DMBA administration, the animals were euthanized. There was a delay in the development of breast tumor in the α-lactalbumin group in comparison to the casein group. The number of tumors per rat was less in the α-lactalbumin group than that in the casein group at any time point up to 130 days after DMBA administration. Also the incidence of tumors and tumor volume was less in the α-lactalbumin group than those in the casein group. The casein group had a mixture of grade I, grade II and grade III tumors whereas the α-lactalbumin group had mostly grade I tumor. Furthermore, the proliferative index was significantly lower in the α-lactalbumin group than that in the casein group.

Evaluation of the protective effect of Nigella sativa extract and its primary active component thymoquinone against DMBA-induced breast cancer in female rats.

IntroductionThe historical use of black cumin seed (Nigella sativa) dates back centuries, being embedded in Arabian culture and having a long history of unsurpassed medicinal value with versatility to treat a wide range of ailments. Thymoquinone (TQ) is now known to be the primary active constituent of black cumin seed oil (BCS oil) responsible for its medicinal effects and also showing promise for treatment of cancer.Material and methodsIn the current study, we have studied the effects of TQ and BCS oil on tumor markers (MDA, LDH, ALP and AST), histopathological alterations and the regulation of several genes (Brca1, Brca2, Id-1 and P53 mutation) related to breast cancer in female rats induced by 7,12-dimethylbenz[a]anthracene (DMBA) treatment. Rats received a single dose (65 mg/kg b.w.) of DMBA via an intragastric tube to induce breast cancer. Animals that received DMBA were treated orally with 1, 5, 10 mg/kg of TQ or BCS oil via an intragastric tube three times per week for 4 months.ResultsWe found that TQ and then BCS reduced the rate of tumor markers (levels of MDA and LDH as well as ALP and AST activities), inhibited the histopathological alterations and decreased the expression of the Brca1, Brca2, Id-1 and P53 mutations in mammary tissues of female rats induced by DMBA treatment.ConclusionsThe results suggest that TQ and BCS oil exert a protective effect against breast carcinogens. The antioxidant property of TQ and BCS oil is mediated by their actions and investigating other underlying mechanisms merits further studies.

Quercetin in Dimethyl Benzanthracene Induced Breast Cancer in Rats

Problem statement: Vincristine a commonly used anticancer agent in th e treatment of breast cancer results in serious adverse effects li ke teratogenicity, neurotoxicity and carcinogenicit y on long term use. Drug resistance is also a common pro blem encountered with vincristine. Hence the effect of flavonol quercetin, a known antioxidant w ith no known documented adverse effect was tried in treatment of DMBA induced breast cancer in female rats and its effect was compared with vincristine. Approach: Quercetin at the dose of 50, 100-200 mg kg -1 body weight was administered in DMBA induced breast cancer in female wistar rats and its effects were compared with Vincristine. The anti oxidant enzymes, catalase, glutathione peroxid ase and superoxide dismutase and Thiobarbituric Acid Reactive Substances (TBARS) level in cancerous breast tissue, TBARS and catalase in plasma and superoxide dismutase and glutathione peroxidase in erythrocyte lysate were estimated. Results: Quercetin supplementation at the dose of 100 mg kg -1 body weight was most effective in alleviating cancer symptoms and was comparable to vincristine. The plasma TBARS were reduced and breast tissue TBARS were elevated. The antioxidant enzymes were rejuvenated by quercetin supplementation at all three dose levels. Conclusion: Quercetin is found to be an effective chemotherape utic agent in the treatment of breast cancer on par with vincrist ine. Being a plant product, quercetin can also be u sed in chemoprophylaxis in high risk individuals with g enetic predisposition towards breast cancer. Besides, it can be given orally and has a wide marg in of safety.

Comparative study on the effects of crocin, crocetin and picrocrocin on NMU-induced breast cancer in female rats

Comparative study on the effects of crocin, crocetin and picrocrocin on NMU-induced breast cancer in female rats

Oral administration of loquat suppresses DMBA-induced breast cancer in rats

This study was to demonstrate whether loquat leaves protect against 7,12-dimethylbenz[α]anthracene (DMBA)-induced breast cancer in female rats. Rats were fed control diet (NC, DC), ethanol (DE), or water extract of loquat leaves (DW) until sacrifice. At 50 days of age, animals in the DC, DE, and DW groups were given a single intra-gastric dose of DMBA (50 mg/kg) dissolved in corn oil. Both the water and ethanol extracts of loquat leaves decreased the incidence of tumors, with water extract having the higher inhibitory effect. Ethanol extract significantly decreased the multiplicity of tumors. Loquat extracts significantly decreased tumor cell proliferation and the tumor grade based on the degree of tubule formation. These results suggest that both water and ethanol extracts of loquat leaves inhibit the development of breast cancer. Such inhibition may be based on the suppression of initiation and tumor cell proliferation.

Abstract 1687: Carcinogen induced inflammation and pancreatic cancer

Abstract National Toxicology Program (NTP) performs two-year cancer bioassays. We have analyzed the NTP rat data base and searched for gender differences in susceptibility to carcinogens. We identified 10 chemicals that induced exocrine pancreatic cancer in male rats only, but found no chemical that induced pancreatic cancer in female rats only. Furthermore, males were most affected by three chemicals that induced pancreatic cancer in both sexes. In an effort to understand this sex difference in susceptibility, we used a tool which builds on the technology published in BMC Bioinformatics 2009, 10, 303. This tool was built to assist cancer risk assessors in the analysis of literature data on modes of action (MOA). We used this tool in the analysis of 2041 PubMed abstracts on the 10 male-specific carcinogens. The tool automatically selected 634 abstracts as relevant for cancer and sorted them in taxonomies. The sorting suggested that induction of oxidative stress and inflammation was a common feature among the 10 carcinogens. As chronic pancreatitis is a risk factor for human exocrine pancreatic cancer, we investigated the effects of the 10 carcinogens on Ca2+ signaling and on inflammatory markers in pancreatic cancer cell line Panc-1. It was found that many the 10 male specific carcinogens rapidly increased intracellular [Ca2+] and interfered with extracellular ATP-induced Ca2+ release in Panc-1 cells. The effect on [Ca2+] was followed by activation of calcineurin and phosphorylation of Erk. Some of these effects were blocked by inhibitors of the purinergic P2X7 receptor, a receptor which may rapidly increase intracellular [Ca2+]. We further studied the induction of mRNA levels of inflammatory mediators, and found that IL8 was significantly up-regulated by most of the 10 chemicals. Our data suggest that inflammation is important for chemically induced exocrine pancreatic cancer in the rat and that male rats are more susceptible. Our data may have a bearing on human pancreatic cancer as men, and in particular young men, have a higher incidence of pancreatic cancer than women. Increased levels of the P2X7 receptor has also been detected in chronic pancreatitis in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1687.