Dimethylbenzanthracene Research Articles

Therapeutic Effects of Ginseng and Doxorubicin on DMBA-Induced Ovarian Cancer in Wistar Rats

ABSTRACT Background Ovarian cancer can be attributed to various external factors, such as tobacco use, exposure to chemicals and radiation, and infections. Internal factors, including inherited mutations, hormonal factors, immune conditions, and random mutations, also play a role in its development. Exposure to carcinogen such as 7,12 Dimethyl Benz Anthracene can induce ovarian cancer. The aim of the study is to investigate the effect of Ginseng and Doxorubicin on Ovotoxicity induced by DMBA in Wistar rat. s Methods A total number of twenty-five females (25) wistar rats which average weight was 135g were used and the animals were randomly split into five groups (A, B, C, D, E) with each group comprising of five rats. Group A (served as the control) given physiological saline only, Group B were induced with 7,12 Dimethyl Benz Anthracene and post treated with Ginseng (50 mg/kg) (GIN). Group C were induced with 7,12 DMBA and post treated with Doxorubicin (25mg/kg). Group D were induced with 7,12 DMBA and post treated with Doxorubicin (25 mg/kg) and Ginseng (50 mg/kg). Group E were induced with 7,12 Dimethyl Benz (a) Anthracene (DMBA) (50mg/kg). Drug administration was done orally using oral cannula and intramuscularly using syringe and needle. Results Ovary histoarchitecture for control group A, B (GIN group), and D (DOX+GIN group) revealed intact organization and structure of the ovary. In these groups, no observable pathological changes were seen as the ovaries were characterized with the presence of numerous follicular cells with a normal and well-defined cellular density. For C (DOX group), the histoarchitecture showed a localized collection of blood outside the blood vessels, typically resulting from a ruptured blood vessel (hematoma of blood vessels) and slight degenerative changes in the ovary. For E (DMBA group), showed atrophied and atretic ovarian cells, necrotic oocyte, severe degenerative changes were also observed. For Hormonal analysis, there was a significant decrease in Serum FSH & LH concentration in DMBA treated group compared to the Ginseng and control groups. Conclusions DMBA evidently induced ovarian toxicity, and its effects were efficiently attenuated by the use of Ginseng and Doxorubicin.

Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer

Background: Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin- E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated. Methods: The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin- E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin- E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined. Results: The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 μg/ml. LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors. Conclusions: These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.

Anti-tumor property of Argemone mexicana leaves methanol extracts against 7, 12- Dimethylbenz[a]anthracene (DMBA) induced mammary tumors in experimental rats

Background: Breast cancer is a complex and multistage process. Many natural compounds are available for an effective and efficient alternative method against breast cancer. This study focused on the anti-cancer activity of Argemone mexicana leaf extract on Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in experimental rats. Materials and Methods: Argemone mexicana Leaves (AML) were collected, extracted by soxhlet apparatus with methanol solvent, and analyzed by Gas Chromatography and Mass-Spectroscopy (GCMS). Healthy Female Sprague-Dawley rats (7-8 weeks and 100 ± 20 g) were divided in five groups and used to induce mammary tumors by DMBA [25 mg/kg/ Subcutaneous (s.c.)]. After developing a palpable nodule (10-12 weeks after DMBA), the rats were treated with AML extract [200 and 400 mg/kg/Body Weight (b.w.)] and Tamoxifen (TAM 10 mg/kg) orally for 12 weeks. Body weight, tumor weight and volume measurements, lipid peroxidation, antioxidant and tumor marker [Carcinoembryonic Antigen (CEA)] levels, and histological investigations were assessed. Results: Following AML treatment, there was a reduction in weight and volume (P< 0.01) of breast tumor, as well as a significant decrease in levels of lipid peroxidation and tumor marker CEA (P < 0.001) and improved Superoxide Dismutase (SOD), Reduced glutathione (GSH), and caspase levels (P < 0.001). In cytological results, AML improved the cellular architecture, and significant restoration in histopathological examinations revealed a tumor with minimal glandular epithelium proliferation, a decrease in mitotic figures, and nuclear alterations. Conclusion: The study suggests that AML extract has a chemoprotective effect against DMBA-induced mammary tumors in experimental animals, specifying its possibility as a therapeutic agent for breast cancer treatment.

Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat

Objective In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). Materials and methods The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. Results After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). Conclusions These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Therapeutic effects of tilorone on mammary carcinogenesis through downregulation of pro-inflammatory cytokines and oxidative stress.

Tilorone dihydrochloride (tilorone) is an orally active interferon inducer with anticancer effects. The present study aimed to evaluate the anticancer effects of tilorone in breast cancer. MTT assay was done to measure the proliferation of MCF-7 and MDA-MB-231 breast cancer cells after treatment with tilorone. Mammary carcinogenesis was induced by subcutaneous injection (35 mg/kg, 0.5 mL) of dimethylbenz[a]anthracene (DMBA) in mammary pads of Sprague Dawley (SD) rats. Tumors were allowed to grow for 16 weeks till their sizes reached to 550-700 mm3, and then treated with 10 and 20 mg/kg of tilorone and standard drug doxorubicin (4 mg/kg) twice a week for 3 weeks. Normal and disease-control animals received normal saline. Tumor volumes and body weights were measured. Tumors were isolated to measure the levels of interferon-β (IFN-β), vascular endothelial growth factor-A (VEGF-A), P53 and inflammatory markers by enzyme-linked immunosorbent assay (ELISA). Serum biochemistry, lipid peroxidation (LPO) and antioxidant enzymes were measured by standard methods. Histopathology and immunohistochemistry (IHC) of P53 was done in tumor sections. Tilorone reduced the proliferation of MCF-7 and MDA-MB-231 cells with IC50 concentrations at 34.08 µM and 14.27 µM, respectively. Tilorone treatment showed reduced tumor volume, and increased survival with no significant changes in the body weights. Tilorone treatment also decreased levels of inflammatory markers and VEGF-A and increased IFN-β and P53 levels. Further, treatment with tilorone also decreased LPO and increased antioxidants levels. Histopathology of tumor sections showed normalizing morphology of treated animals. IHC of tumor sections showed increased levels of P53. In conclusion, tilorone has potential anticancer effects against breast cancer.

Valsartan as a prophylactic treatment against breast cancer development and niche activation: What molecular sequels follow chronic AT-1R blockade?

AimsTransactivation of insulin-growth-factor-receptor (IGF-1R) by angiotensin-II-type-1-receptor (AT-1R) was only demonstrated in vascular-smooth-muscle cells and has never been tested in breast-cancer (BC). This investigation addressed the impact of chronic AT-1R blockade by valsartan (Val) on possible concurrent AT-1R/IGF-1R signaling inhibition, regressing BC-tumor-microenvironment (TME) cellular components activation, and hindering BC development. Main methodsThe effect of different Val doses (10, 20, 40 & 80 mg/kg/day for 490 days) was tested on dimethylbenz(a)anthracene (DMBA)-induced progesterone-promoted-BC in rats. The influence on intratumoral/circulating angiotensin-II (ANG-II) levels and AT-1R/Mas-R immunofluorescent-expression were assessed. The potential AT-1R/IGF-1R crosstalk within TME-BC-stem-cells (BCSCs) and cancer-associated-fibroblasts (CAFs) was evaluated by fluorescently marking these cells and locating the immunofluorescently-stained AT-1R/IGF-1R in them using confocal-laser-microscopy and further quantified by flow cytometry. In addition, the molecular alterations following blocking AT-1R were inspected including determining Src; crucial for IGF-1R transactivation by AT-1R, Notch-1; IGF-IR transcriptional-regulator, and PI3K/Akt &IL-6/STAT expression. Further, the suppression of CSCs' capabilities to maintain pluripotency, stemness features, epithelial-to-mesenchymal-transition (EMT), and angiogenesis was evaluated by assessing NANOG gene, aldehyde-dehydrogenase (ALDH), N-cadherin and vascular-endothelial-growth-factor (VEGF), respectively. Furthermore, the proliferative marker; Ki-67, was detected by immunostaining, and tumors were histologically graded using Elston-Ellis-modified-Scarff-Bloom-Richardson method. Key findingsProphylactic Val significantly reduced tumor size, prolonged latency, reduced tumor histopathologic grade, decreased circulating/intratumoral-ANG-II levels, increased Mas-R, and decreased AT1R expression. AT-1R/IGF-1R were co-expressed with a high correlation coefficient on CAFs/BCSCs. Moreover, Val significantly attenuated IGF-1R transactivation and transcriptional regulation via Src and Notch-1 genes' downregulation and reduced Src/IGF-IR-associated PI3K/Akt and IL-6/STAT3 signaling. Further, Val significantly decreased intratumoral NANOG, ALDH, N-cadherin, VEGF, and Ki-67 levels. SignificanceChronic Val administration carries a potential for repurposing as adjuvant or conjunct therapy for patients at high risk for BC.

Efficacy of Different Doses of Quercetin against Chemically Induced Oral Squamous Cell Carcinoma in Hamsters

Abstract Background: The use of Caspase-3 to evaluate the chemopreventive effect of quercetin on experimentally induced squamous cell carcinoma was applied in the current study. Materials and Methods: Five groups of Syrian male hamsters were employed in the study. Group I (negative control): 5 animals do not receive any treatment. Group II: 5 animals receiving (quercetin only at a concentration of 150 mg/kg). Group III (dimethylbenz(a)anthracene [DMBA]-treated group for 14 weeks): 10 animals were coated with 0.5% DMBA. Group IV (DMBA + quercetin 150 mg/kg): 15 animals receiving quercetin of a concentration (150 mg/kg) every day through a gavage tube along with painting the hamster buccal pouch with DMBA (0.5%) three times per week for 14 weeks. Group V (DMBA + quercetin 50 mg/kg): 15 animals receiving quercetin of concentration (50 mg/kg) every day through a gavage tube along with painting the hamster buccal pouch with DMBA (0.5%) for 14 weeks at three times each week. Results: Group III showed the lowest mean area percent (10.23), whereas Group V revealed the highest mean area percent value (23.64). All groups showed a statistically significant difference among them. Conclusion: Quercetin showed apoptotic potential validated by Caspase-3, so it may be a valuable chemopreventive agent antagonizing DMBA-induced carcinogenesis in animal models.

Novel composite fatty acid vesicles-in-Pluronic lecithin organogels for enhanced magnolol delivery in skin cancer treatment

A novel composite carrier composed of Pluronic lecithin organogels and fatty acid vesicles was used to enhance the stability and facilitate the topical delivery of a natural bioactive drug, magnolol (Mag), for treatment of skin cancer. Jojoba oil was incorporated in the organogel (OG) base to provide a synergistic effect in treatment of skin cancer. The organoleptic properties, rheological behavior, morphology, and drug content of the OG formulations were investigated with emphasis on the impact of vesicle loading on the OG characteristics. The effect of OG on Mag release and ex-vivo permeation studies were evaluated and compared to free Mag in OG. The biological anti-tumor activity of the OG formulae was assessed using a skin cancer model in mice.All OG formulations exhibited uniform drug distribution with drug content ranging from 92.22 ± 0.91 to 100.45 ± 0.77 %. Rheological studies confirmed the OG shear-thinning flow behavior. Ex-vivo permeation studies demonstrated that the permeation of Mag from all OG formulations surpassed that obtained with free Mag in the OG. The anti-tumor activity studies revealed the superior efficacy of 10-hydroxy-decanoic acid (HDA)-based vesicles incorporated in OG formulations in mitigating 7,12- dimethylbenz(a)anthracene (DMBA)-induced skin cancer, thereby offering a promising platform for the local delivery of Mag.

Impact of coconut kernel extract on carcinogen-induced skin cancer model: Oxidative stress, C-MYC proto-oncogene and tumor formation

This study aimed at analysing the effects of coconut (Cocos nucifera L.) kernel extract (CKE) on oxidative stress, C-MYC proto-oncogene, and tumour formation in a skin cancer model. Tumorigenesis was induced by dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA). In vitro antioxidant activity of CKE was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), total phenolic and flavonoid content assays. CKE showed a higher antioxidant activity then ascorbic acid (*P < 0.05, ****P < 0.0001). HPLC and NMR study of the CKE revealed the presence of lauric acid (LA). Following the characterization of CKE, mice were randomly assigned to receive DMBA/TPA Induction and CKE treatment at different doses (50, 100, and 200 mg/kg) of body weight. LA 100 mg/kg of body weight used as standard. Significantly, the CKE200 and control groups' mice did not develop tumors; however, the CKE100 and CKE50 treated groups did develop tumors less frequently than the DMBA/TPA-treated mice. Histopathological analysis revealed that the epidermal layer in DMBA-induced mice was thicker and had squamous pearls along with a hyperplasia/dysplasia lesion, indicating skin squamous cell carcinoma (SCC), whereas the epidermal layers in CKE200-treated and control mice were normal. Additionally, the CKE treatment demonstrated a significant stimulatory effect on the activities of reactive oxygen species (ROS), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), as well as an inhibitory effect on lipid peroxidase (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001) and c-MYC protein expression (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). In conclusion, CKE prevents the growth of tumors on mouse skin by reducing oxidative stress and suppressing c-MYC overexpression brought on by DMBA/TPA induction. This makes it an effective dietary antioxidant with anti-tumor properties.

High fructose Corn Syrup recast glucose transporter-5, Wnt, NF-κB signalling and mitochondrial apoptosis in an animal model of oral oncogenesis

BackgroundWnt signalling pathway, is mediated by members of T-cell factor (TCF) transcription factors family, is essential for the control of epithelial cell proliferation and death. Glucose transporter-5 (GLUT5), fructose-specific transporter, is also important in allowing transcellular fructose uptake. The goal of this work to determine how the High fructose Corn Syrup (HFCS) affected Wingless-related integration site (Wnt) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in the 7,12 –dimethylbenzaanthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs) model. MethodsFour groups of hamsters were created. For 12 weeks, 0.5 % DMBA was applied 3 times/week to the left side buccal pouches of the hamsters in groups (2 & 4). Additionally, the animals in groups (3 & 4) were given through drinking water of HFCS 25 %. The control animals were from group 1. By using western blot analysis, signalling network markers of the GLUT-5, Wnt, TCF-4, GSK-3β and NF-κB as well as mitochondrial apoptotic pathway marker expression B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cyclooxygenase – 2 (COX-2) was assessed. ResultsDrinking water uptake of 25% HFCS encouraged progress of HBP carcinomas by constitutive stimulating of the Wnt pathway via GSK-3β overexpression. HFCS suppressed Wnt signalling which contributed the NF-κB attenuation and changes the signalling markers in apoptotic network. ConclusionsOur hypothesis suggests a mechanically crosstalk between Wnt and NF-κB signalling pathways in HBP carcinomas that is developed by HFCS. HFCS that targets the Wnt pathway and its downstream signalling mediators could be additive reason for cancer development.

Assessment of Anticancer Activity of Crude Ethanolic Extracts of Moringa Oleifera Pod and Leaves on 7,12 - Dimethylbenz Anthracene Induced Skin Cancer in Mice.

Background and Objective: Carcinoma of the skin is the commonest cancer in the world. This study aims to assess the anti-cancer effect of the ethanolic pod and leaf extracts of Moringa Oleifera on 7,12 - dimethylbenz anthracene (DMBA) induced skin carcinoma in mice. Methodology: Animals were divided into 6 groups of 5 each. 7,12 - dimethylbenz anthracene (DMBA) was used topically for four weeks to induce tumour. Group 1 received placebo, Group 2 - standard drug 5- Fluorouracil, Groups 3, 4 received pod extract and Groups 5,6 received leaf extract of Moringa Oleifera of concentration 500 and 1000mg/kg respectively for 3 weeks. Hematological and biochemical parameters such as Hemoglobin, RBC, WBC and platelet counts, SGOT and SGPT, blood urea nitrogen and serum creatinine were done before cancer induction and at the end of 7 weeks. Histopathological examination of the skin, liver and kidney were done at the end of 7 weeks. Results: There was reduction in tumor size in the Moringa Oleifera pod and leaf extract treated groups. Histopathology revealed infiltration of the cells with scarring of epidermis in the extract treated groups indicating the healing of tissues more pronounced at higher concentration. Control group showed atypical squamous cells whereas the standard drug treated group showed infiltration and scarring. Conclusion: This study exhibits a dose dependent anticancer effect of Moringa oleifera pod and leaf extracts in mice which was comparable with the standard drug 5-Fluorouracil.

Phytochemical characterization and assessment of antitumor activity of the aqueous extract of Acmella caulirhiza in female Wistar rats induced by 7,12 dimethylbenz (a) anthracene

BackgroundRecent studies increasingly show the implication of medicinal plants in cancer management. Acmella caulirhiza, a plant belonging to the Asteraceae is traditionally used as an analgesic and anti-inflammatory agent to fight against diseases like cancer. Purpose: This study aimed to evaluate the antitumoral properties of the aqueous extract of leaves and flowers of A. caulirhiza (AE-Ac). MethodsAfter phytochemical characterization, the cytotoxic activity of AE-Ac on MCF-7 breast cancer lines was carried out using the MTT method. For in vivo study, 36 female Wistar rats (6 weeks old) were randomly divided into 6 groups (n = 6 each) as follows: normal control receiving distilled water (NC), positive control receiving distilled water (DMBA), 3 test groups (receiving either 75, 150 or 300 mg/kg.Bw of AE-Ac (AE-Ac 75, AE-Ac 150 and AE-Ac 300 respectively)) and a reference group (Tam) receiving Tamoxifen at 3.3 mg/kg.Bw. They were fed with a high-fat diet daily. After 2 weeks all groups except the NC group were treated with a single dose of DMBA (7,12-Dimethylbenz (a) anthracene) (50 mg/kg. Bw) by intraperitoneal injection. Daily treatments were administered by intragastric intubation for 12 weeks. At the end, animals were sacrificed after 12 h of fasting and blood was collected for biochemical analysis. The mammary glands were isolated for histological analysis. ResultsAE-Ac contains bioactive compounds amongst which stigmasterol, phytol, ellagic acid, phenol, sterols, alkaloids, flavonoids. AE-Ac was more active at 72 h (IC50 = 114.86 µg/mL) on MCF-7 cells. The cancer-treated groups exhibited the lowest percentage of weight gain variation, particularly the group receiving the reference molecule (Tamoxifen) (68.12 %) followed by the AE-Ac 150 group (92.45 %). AE-Ac at 150 and 300 mg/kg-Bw significantly reduced tumor volume and CA 15-3 levels (p = 0.004). Histological analysis of the mammary gland revealed more extensive ascini destruction in the AE-Ac 75 group followed by the DMBA group. Treatment with the 150 mg/kg.Bw ameliorated antioxidant enzyme (SOD and Catalase (p < 0.001)) activities, pro-oxidant levels (NO● and HO●), as well as inflammatory parameters (TNF-α and EGF; RBC, Hb, PLT) (p < 0.05). ConclusionThese results suggest that AE-Ac can be a good candidate as a complementary agent in breast cancer management.

Thrombocytopenia and Non-Expression of Tn And TF Antigens Define Non-Metastasizing Breast Cancer in Serial Transplants of Dimethyl Benz(A)Anthracene Induced Mammary Tumours in Sprague Dawley Rats

Functional mammary tumours were generated as serial transplants of dimethyl benz(a)anthracene (DMBA) in immunosuppressed Sprague Dawley rats (SD). These serial transplants were evaluated for their cellular behaviour and biomarkers. Breast cancer was induced by 10 mg/kg of 7, 12 dimethylbenzanthracene (DMBA) in 10 female SD rats. Following tumour development, the primary tumour was passaged into apparently healthy rats for first and second serial transplants. Cellular behaviour and biomarkers of transplants included growth of tumour, haematological indices, expression pattern of Tn and TF antigens and TNF-alpha. An elevation of TNF-α, non-induction of Tn antigen with thrombocytopenia were observed in the serial transplants derived from a malignant tumour induced by 7, 12, DMBA in female Sprague Dawley rats. Furthermore, neutrophil to lymphocyte and platelet to lymphocyte ratios were found to be significantly low in animals from the first serial transplant while being significantly high in animals of the second serial transplant group. Results indicate that DMBA-induced mammary tumours in Sprague Dawley rats undergo divergent cellular behaviour and antigenic expressions during serial transplantation.

Potential chemopreventive effects of Broccoli extract supplementation against 7, 12 dimethyl Benz(a)anthracene (DMBA) -induced toxicity in female rats

Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases after exposure to environmental toxicants. 7, 12 dimethylbenz(a)anthracene (DMBA) is one of the most common environmental pollutants. The present study aimed to evaluate the chemo-preventive effects of broccoli as a nutritional component against DMBA intoxication in rats. A daily dose of aqueous (1 ml/rat) and methanolic (150 mg/kg) broccoli extracts, respectively, was given to 50-day-old female rats for 26 successive weeks after carcinogen intoxication with a single dose of 20 mg/ml of DMBA. DMBA intoxication resulted in a redox imbalance (a decreased GSH level and an increased MDA level) and increased DNA fragmentation in the liver, kidney, and brain. Besides, it affected the level of expression of the bcl2 gene in the liver, kidney, and brain tissue but didn’t affect cfos gene expression accompanied by histopathological changes. The aqueous and methanolic broccoli extract supplements ameliorated the adverse effects by increasing the level of GSH, decreasing the MDA level, and reducing DNA fragmentation. Besides, broccoli extracts decreased the expression of bcl2 in the liver and brain and up-regulated bcl2 expression in the kidney, accompanied by lowering NF-κβ 65 expression in the liver and brain and γ-catenin expression in the liver and kidney. In conclusion, broccoli as a dietary component had a strong chemoprotective effect against oxidative stress, DNA damage, and genotoxicity induced by DMBA intoxication in rats.

Predicted no-effect concentration for eight PAHs and their ecological risks in seven major river systems of China

The initial step in the assessment of the ecological risk of pollutants is to determine the predicted no-effect concentration (PNEC). However, ecological risk assessments of eight carcinogenic polycyclic aromatic hydrocarbons (PAHs), including dimethylbenz[a]anthracene (DMBA), methylcholanthrene (MCA), benzo(a)anthracene (BaA), chrysene (CHR), benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF), benzo(a)pyrene (BaP), and dibenzo(a,h)anthracene (DBA), are rarely conducted due to the lack of their PNECs based on test data. In this study, quantitative structure-activity relationship (QSAR) models and interspecies correlation estimation (ICE) models were combined to predict the acute toxicity of these eight target PHAs. A Kolmogorov–Smirnov analysis for species sensitivity distributions (SSDs) of native and all species was conducted. There was no significant difference between the predictions for native Chinese species and the predictions for all species by the QSAR-ICE models. In addition, the feasibility of the QSAR-ICE models was demonstrated by comparing the SSD curves constructed by measured toxicity data of BaP and those predicted by the QSAR-ICE models. The PNECs of the eight PAHs were estimated based on the SSDs and acute to chronic ratio (ACR) method; these data were 0.071 μg/L, 0.033 μg/L, 0.049 μg/L, 0.114 μg/L, 0.019 μg/L, 0.021 μg/L, 0.038 μg/L and 0.054 μg/L for DMBA, DBA, BaP, MCA, BaA, CHR, BbF, BkF, respectively. The higher PNECs of the alkylated PAHs suggested their lower ecological risks. Based on the mixed risk quotient (mRQ) of PAHs through the concentration addition (CA) model, high ecological risk watersheds, such as the Songhua River (mRQ = 1.95), the Liao River (mRQ = 4.59), and the Huai River (mRQ = 1.93), were identified.

7, 12- Dimethylbenz[a]anthracene: A potent and multivariant Chemical carcinogen

Cancer is currently the second major cause of mortality globally. It is a collection of disorders categorized as abnormal cell development which can infiltrate and can spread to countless sections of the body. It has been essentially brought about by genetic and environmental sources mainly, countless patients have impacted by ecological factors like polycyclic aromatic hydrocarbons (PAHs). However, many PAHs in the ecosystem are generated from natural factors like direct combustion, petroleum and volcanic activity. Among these, 7,12 dimethylbenz[a]anthracene (DMBA) has been widely recognized for its capability to induce carcinogenesis in animals and humans. The carcinogenic activity of DMBA indicates the impact of well-differentiated tumors and it is recognized for generating DNA-reactive species that increase the oxidative damage in cells through their metabolism. Additionally, the configuration of DNA adducts and oxidative intermediates acquired from DMBA metabolism impairs prominent cellular activities by harming lipid and protein barriers. DNA adduct is made up of highly reactive intermediates. DMBA-induced cancer displayed higher expression of aryl hydrocarbon receptor (AhR), c-Myc, cyclinD1, activation of upstream regulatory mechanisms and frequent detection of NF-κB pathway components. In this study, we emphasized the growth of several cancers and the kinetic impact of DMBA to probable chemical carcinogenic activities.

Effect Difference of Centella asiatica Leaves Methanolic Extract on Scratch and Incision of Dimethylbenz [A] Anthracene (DMBA) Induced Dysplasia Incidence

Oral epithelial dysplasia is an abnormal cytology and architectural change that can develop into oral malignancy with a high mortality rate. Centella asiatica leaves possesses the potential to act as a chemopreventive agent and is known for its relative safety and ease of obtainability. Therefore, this study aimed to determine effect of Centella asiatica leaves extract on dysplasia induced by dimethylbenz [a] anthracene (DMBA) with scratch and incision. The in vivo study involved 21 Wistar rats (Rattus novergicus) divided into three groups. The groups received 2% Centella asiatica leaves methanolic extract orally by force-feeding once daily, from day 1 until day 61. At day 29, dysplasia was induced by scratching the buccal mucosa of each rat using a syringe containing 0.5% DMBA. This was conducted with incision 1 cm in length and half angle in depth, 1 cm in length and 1 mm in depth, and 2 cm in length and 1 mm in depth for groups 1, 2, and 3. Furthermore, the rats were sacrificed, and histopathological analysis was performed using hematoxylin-eosin staining. The degree of dysplasia was assessed using the WHO 2017 classification, and the data were analyzed using the Mann-Whitney test. Meanwhile, the statistical test showed significant difference in the degree of dysplasia for all groups. It can be concluded that Centella asiatica methanolic extract leaves possesses the potential to be a chemopreventive agent in reducing dysplasia levels.

Antioxidant and Antitumorigenic Activities of the Standardized Water Extract From Fruit of Terminalia chebula Retz. var. chebula

Background Terminalia chebula Retz. var. chebula ( T chebula) has been traditionally used as a crude drug for treating various diseases, including skin disorders. This study aimed to investigate the potential antioxidant effects and antitumorigenic activity of an aqueous extract from the fruit of T chebula. Methods The extract's total phenolic content and antioxidant activity were measured using Folin-Ciocalteu, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) tests, respectively. The 2 ´,7 ´-dichlorodihydrofluorescin diacetate assay was employed to evaluate the extract's ability to reduce intracellular reactive oxygen species (ROS) in U-937 human monocytic cell lines which had been treated with hydrogen peroxide for 30 min. Male ICR mice ( n = 30, 5 groups) were used to investigate the influence of T chebula extract on dimethylbenz[a]anthracene (DMBA)/12- O-tetradecanoylphorbol 13-acetate (TPA)-induced carcinogenesis. After 20 weeks of treatment with T chebula extract, tumor incidence, size, and number were assessed. The major phenolic compounds in the extract were determined using high-performance liquid chromatography. Statistical analysis was performed using ANOVA followed by post hoc least significant difference test. Results T chebula extract effectively reduced intracellular ROS and scavenged antioxidants in vitro. The IC50 values of the extract as measured by DPPH and FRAP assays were 109.0 ± 14.5 μg/mL and 2.39 ± 0.17 μg/mL, respectively. Moreover, 4 mg of T chebula extract significantly decreased the incidence, volume, and number of tumors in DMBA/TPA-induced skin tumorigenesis in mice. Conclusion T chebula extract effectively reduced intracellular ROS, and significantly decreased the incidence, volume, and number of tumors in DMBA/TPA-induced skin tumorigenesis in mice. These findings suggest that T chebula extract could be a promising therapeutic agent for skin tumors and other oxidative stress-related diseases.

Anticancer role of mango (Mangifera indica L.) peel and seed kernel extracts against 7,12- dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rats

Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague–Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-β estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.

Evaluation of Anti-Carcinogenic Effect of Selenium Nanoparticles on Induced Oral Squamous Cell Carcinoma

Purpose: Current study proposed to estimate the anticarcinogenic influence of Selenium Nanoparticles (SeNps) on induced squamous cell carcinoma utilizing caspase3 as an apoptotic marker. Material and Methods: Thirty hamsters were used, divided into four groups. Group I: 2 hamsters were left untreated, Group II: 8 hamsters received SeNPs orally for 14 weeks at dosage of 0.5 mg/kg on alternative day along the experimental period. Group III: 10 hamsters received Dimethylbenz [a]anthracene (DMBA) (0.5%) painted by brush on the buccal pouch 3 times per week for 8 weeks, then received DMBA with 5-Fluorouracil (5-FU) for another 6 weeks twice a week at dosage of 12.5 mg/kg and continued on 5-FU treatment for another 2 weeks after stop of DMBA. Group IV: 10 hamsters received DMBA alone for 4 weeks. Then received DMBA along with SeNPs for 10 weeks at dosage of 0.5 mg /kg on alternative days to DMBA, continued on SeNPs treatment for another 2 weeks after stop of DMBA. Results: Comparing all groups according to caspase 3 expression revealed that the mean area percentage values have been arranged with the following descending pattern group III, group IV, group I then group II. ANOVA test showed a statistically significant variance between groups, with no statistically significant difference between group I and group II together showed the statistically significant lowest mean area percent values or group III and group IV together showed statistically significant highest mean area percent values. Conclusion: Chitosan coated SeNPs is a promising anticarcingenic agent with less toxicity on healthy tissues at the same time less cancer cell resistance compared to chemotherapeutic drugs.