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Molecules (Basel, Switzerland) Jan 2022Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, -aminophosphonates, arylidine...
Investigation of the Anticancer Effect of -Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2()-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.
Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, -aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2()-one, DMBA, DMBA & -aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2()-one. New -aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2()-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with -aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2()-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2()-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2()-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Caco-2 Cells; Computer Simulation; Drug Evaluation, Preclinical; Female; Fishes; Humans; Mammary Neoplasms, Experimental; Models, Molecular; Molecular Docking Simulation; Molecular Targeted Therapy; Organophosphonates; Plant Extracts; Quinolines; Rats; Thymidylate Synthase
PubMed: 35164019
DOI: 10.3390/molecules27030756 -
International Journal of Molecular... Jan 2022Endocrine-disrupting chemicals (EDCs)-including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)-can...
Endocrine-disrupting chemicals (EDCs)-including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)-can interfere with the endocrine system and produce adverse effects. It remains unclear whether pubertal exposure to low doses of BBP, PFOA, and ZAL has an impact on breast development and tumorigenesis. We exposed female Sprague Dawley rats to BBP, PFOA, or ZAL through gavage for 21 days, starting on day 21, and analyzed their endocrine organs, serum hormones, mammary glands, and transcriptomic profiles of the mammary glands at days 50 and 100. We also conducted a tumorigenesis study for rats treated with PFOA and ZAL using a 7,12-dimethylbenz[a]anthracene (DMBA) model. Our results demonstrated that pubertal exposure to BBP, PFOA, and ZAL affected endocrine organs and serum hormones, and induced phenotypic and transcriptomic changes. The exposure to PFOA + ZAL induced the most phenotypic and transcriptomic changes in the mammary gland. PFOA + ZAL downregulated the expression of genes related to development at day 50, whereas it upregulated genes associated with tumorigenesis at day 100. PFOA + ZAL exposure also decreased rat mammary tumor latency, reduced the overall survival of rats after DMBA challenge, and affected the histopathology of mammary tumors. Therefore, our study suggests that exposure to low doses of EDCs during the pubertal period could induce changes in the endocrine system and mammary gland development in rats. The inhibition of mammary gland development by PFOA + ZAL might increase the risk of developing mammary tumors through activation of signaling pathways associated with tumorigenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Caprylates; Carcinogenesis; Cell Transformation, Neoplastic; Endocrine Disruptors; Female; Fluorocarbons; Hormones; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Phthalic Acids; Rats; Rats, Sprague-Dawley; Zeranol
PubMed: 35163327
DOI: 10.3390/ijms23031398 -
Biomedicine & Pharmacotherapy =... Mar 2022Naturally occurring phytochemicals especially polyphenolic compounds have received increasing attention as chemopreventive agents. The chemopreventive potential of the...
Naturally occurring phytochemicals especially polyphenolic compounds have received increasing attention as chemopreventive agents. The chemopreventive potential of the ethanolic extract of Salvadora persica L. fruits SP, (the arak tree or miswak) on 7,12-dimethylbenz (a) anthracene (DMBA)-induced mammary carcinogenesis in female albino rats was investigated in this work. Ethanolic extract of SP fruits was supplemented to the experimental groups at a concentration of 500 mg/kg body weight for 22 weeks. Administration of SP extract suppressed DMBA-induced mammary carcinogenesis as revealed by incidence of tumors in histological investigation. There was a significant reduction in cell proliferation and an increase in apoptosis with downregulation of estrogen receptor expression in the mammary tissue of SP-treated animals. Additionally, SP extract prevented the oxidative damage induced in breast tissues of DMBA-treated rats. SP treatment also decreased the viability of MCF-7 breast cancer cells and induced early and late apoptosis and induced S cell cycle arrest. The chemo-preventive properties and anticancer effects of SP could be attributed to its anti-oxidative and a high percentage of phenolic compounds and esters which were detected here in the SP fruit extract.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Cell Proliferation; Down-Regulation; Female; Humans; MCF-7 Cells; Mammary Neoplasms, Experimental; Oxidative Stress; Plant Extracts; Random Allocation; Rats; Rats, Wistar; Receptors, Estrogen; Salvadoraceae; Xenograft Model Antitumor Assays
PubMed: 35124384
DOI: 10.1016/j.biopha.2022.112666 -
Scientific Reports Jan 2022Mammary carcinoma, breast cancer, is the most commonly diagnosed cancer type among women. Therefore, potential new technologies for the diagnosis and treatment of the...
Mammary carcinoma, breast cancer, is the most commonly diagnosed cancer type among women. Therefore, potential new technologies for the diagnosis and treatment of the disease are being investigated. One promising technique is microwave applications designed to exploit the inherent dielectric property discrepancy between the malignant and normal tissues. In theory, the anomalies can be characterized by simply measuring the dielectric properties. However, the current measurement technique is error-prone and a single measurement is not accurate enough to detect anomalies with high confidence. This work proposes to classify the rat mammary carcinoma, based on collected large-scale in vivo S[Formula: see text] measurements and corresponding tissue dielectric properties with a circular diffraction antenna. The tissues were classified with high accuracy in a reproducible way by leveraging a learning-based linear classifier. Moreover, the most discriminative S[Formula: see text] measurement was identified, and to our surprise, using the discriminative measurement along with a linear classifier an 86.92% accuracy was achieved. These findings suggest that a narrow band microwave circuitry can support the antenna enabling a low-cost automated microwave diagnostic system.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Electric Conductivity; Electrodiagnosis; Female; Machine Learning; Mammary Neoplasms, Experimental; Microwaves; Predictive Value of Tests; Rats, Sprague-Dawley; Reproducibility of Results; Rats
PubMed: 35013545
DOI: 10.1038/s41598-021-03884-7 -
BMC Complementary Medicine and Therapies Dec 2021Despite the considerable advances made in the treatment of cancer, it remains a global threat. Tartrazine (E102) is a synthetic dye widely used in food industries; it...
BACKGROUND
Despite the considerable advances made in the treatment of cancer, it remains a global threat. Tartrazine (E102) is a synthetic dye widely used in food industries; it has recently been shown to induce oxidative stress (a well known risk factor of cancer) in rat tissues. The present work therefore aimed to assess the impact of a regular consumption of tartrazine on the incidence of breast cancer in rats.
METHODS
Forty (40) Wistar rats aged 55 to 60 days were randomly assigned into 5 groups (n = 8) including two groups serving as normal controls and receiving distilled water (NOR) or tartrazine (NOR + TARZ). The three remaining groups were exposed to the carcinogen DMBA (50 mg/kg) and treated for 20 weeks with either distilled water (DMBA), tartrazine 50 mg/kg (DMBA + TARZ) or a natural dye (DMBA + COL). The parameters evaluated were the incidence, morphology and some biomarkers (CA 15-3, estradiol and α-fetoprotein) of breast cancer. The oxidative status and histomorphology of the tumors were also assessed.
RESULTS
A regular intake of tartrazine led to an early incidence of tumors (100% in rats that received TARZ only vs 80% in rats that received DMBA only), with significantly larger tumors (p < 0.001) (mass = 3500 mg/kg and volume = 4 cm). The invasive breast carcinoma observed on the histological sections of the animals of the DMBA + TARZ group was more developed than those of the DMBA group. The increase in serum α-fetoprotein (p < 0.05) and CA 15-3 (p < 0.01) levels corroborate the changes observed in tumors. The presence of oxidative activity in animals of the DMBA + TARZ group was confirmed by a significant decrease (p < 0.001) in the activity of antioxidant enzymes (SOD and catalase) as well as the level of GSH and increase in the level of MDA compared to the rats of the DMBA and NOR groups.
CONCLUSION
Tartrazine therefore appears to be a promoter of DMBA-induced breast tumorigenesis in rats through its oxidative potential. This work encourages further studies on the mechanisms of action of tartrazine (E102) and its limits of use.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor; Carcinogens; Carcinoma; Estradiol; Female; Mammary Neoplasms, Experimental; Mucin-1; Organ Size; Oxidative Stress; Rats; Rats, Wistar; Tartrazine; Tumor Burden; alpha-Fetoproteins
PubMed: 34972512
DOI: 10.1186/s12906-021-03490-0 -
The Journal of Investigative Dermatology Jun 2022Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes...
Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes to papilloma formation, we utilized Il13rα1-knockout (KO) mice in a widely used 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl phorbol-13-acetate two-stage skin carcinogenesis protocol that mimics the development of squamous cell carcinoma. KO mice developed more papillomas and significantly faster than wild-type mice. Papilloma development reduced regulatory T cells in wild-type mice but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in wild-type mice but not in KO mice. Furthermore, systemic IL-5 and TSLP levels were elevated, whereas IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear myeloid‒derived suppressor cells were decreased in the KO mice at the early phase of papilloma induction. We show that IL-13Rα1 protects from papilloma development in chemically induced skin carcinogenesis, and our results provide further insights into the protective role of functional IL-4 and IL-13 signaling through type II IL-4 receptor in tumor development.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Interleukin-13; Interleukin-13 Receptor alpha1 Subunit; Mice; Mice, Knockout; Papilloma; Skin Neoplasms; T-Lymphocytes, Regulatory; Tetradecanoylphorbol Acetate
PubMed: 34808240
DOI: 10.1016/j.jid.2021.11.013 -
Molecular Therapy Oncolytics Dec 2021Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory and fatal human malignancies. Leucine-rich repeat neuronal protein-1 (LRRN1) plays a crucial role...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory and fatal human malignancies. Leucine-rich repeat neuronal protein-1 (LRRN1) plays a crucial role in the development of the nervous system. However, the clinical implications and biological functions of LRRN1 in PDAC remain unclear. We found that LRRN1 expression was upregulated in PDAC tissues compared with paracancerous tissues and normal pancreatic tissues through the different public databases, tissue microarray-based immunohistochemistry, and dimethylbenzanthracene-induced PDAC murine model. The expression level of LRRN1 was closely related to the overall survival and disease-free survival of PDAC patients. Cox multivariate analysis indicated that LRRN1 was an independent adverse prognostic factor. The small hairpin RNA (shRNA)-mediated LRRN1 knockdown remarkably restrained the proliferative, migratory, and invasive capacities, as well as promoted cell apoptosis and increased G0/G1 arrest in PDAC cells. The xenograft murine subcutaneous bearing model and metastasis model verified that silencing of LRRN1 effectively dampened tumor growth and metastasis . Specifically, LRRN1 exerted its biological functions through the HIF-1α/Notch signaling pathway, and LRRN1 knockdown could dampen Jagged 1-mediated Notch pathway activation. Therefore, LRRN1 could serve as the potential therapeutic or prognostic target for PDAC.
PubMed: 34632050
DOI: 10.1016/j.omto.2021.08.012 -
Journal of Oleo Science 2021Inflammatory reactions and oxidative stress play a major role in cancer expansion. Boeravinone B (BB) had already proofed their anti-inflammatory and antioxidant effects...
Inflammatory reactions and oxidative stress play a major role in cancer expansion. Boeravinone B (BB) had already proofed their anti-inflammatory and antioxidant effects against various animal models of disease. In this experimental research, the chemoprotective effect of BB against skin cancer caused by 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil was investigated and the possible mechanism was explored. Swiss albino mice were used in the current protocol. 100 µg/100 mL acetone, DMBA was used for induction the skin cancer and, after the 2-week repeated dose of croton oil (1% in acetone) give to the mice till end of the protocol. The mice were received the oral dose of BB (1.25, 2.5 and 5 mg/kg, body weight). The body weight and tumor incidence were estimated at regular time interval. At the end of the protocol, the antioxidant, phase I, phase II, pro-inflammatory cytokines and inflammatory mediators were scrutinized. The mRNA expression of pro-inflammatory cytokines and inflammatory mediators were estimated. BB treatment significantly (p < 0.001) reduced tumor incidence, tumor yield, average latency period and tumor burden in a dose-dependent manner. BB treatment considerably (p < 0.001) reduced the levels of lipid peroxidation (LPO) and increased the level of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) in DMBA/croton-induced skin cancer. BB treatment significantly (p < 0.001) reduced the level of phase I and phase II enzymes. BB treatment considerably reduced the cytokines include tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), interleukin-1β (IL-1β), interleukin-6 (IL-6) and inflammatory parameters such as transforming growth factor beta 1 (TGF-β1), prostaglandin E2 (PGE), nuclear kappa B factor (NF-κB) and cycloxgenase-2 (COX-2) in DMBA/croton-induced skin cancer mice. BB considerably (p < 0.001) reduced the mRNA expression of pro-inflammatory cytokines and inflammatory mediators. The results of the current investigation suggest that oral administration of boeravinone B significantly reduced skin cancer in mice via reduction of inflammatory reaction.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anti-Inflammatory Agents; Antioxidants; Body Weight; Croton Oil; Cytokines; Flavonoids; Inflammation; Inflammation Mediators; Mice; Skin Neoplasms; Tumor Burden
PubMed: 34193671
DOI: 10.5650/jos.ess21055 -
In Vivo (Athens, Greece) 2021The aim of the study was to assess the impact of nano-, micro-, and macro-sized-genistein on the growth and development of neoplasms in rats with mammary cancer....
BACKGROUND/AIM
The aim of the study was to assess the impact of nano-, micro-, and macro-sized-genistein on the growth and development of neoplasms in rats with mammary cancer. Additionally, the effect on the kinetics of changes (9-11-17-20 week of a rat's life) in the levels of methyl derivatives: 1-methyladenine, 3-methyladenine, 7-methylguanine, 1-methylguanine, 1-methyladenosine, 7-methylguanosine, O-methyl-guanosine and N6-methyl-2'-deoxyguanosine in the urine of rats was analyzed.
MATERIALS AND METHODS
Female Sprague-Dawley rats divided into 4 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano-, micro- and macro-sized genistein. To induce the mammary adenocarcinoma, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a high-performance liquid chromatography coupled to mass spectrometry method (LC-MS/MS).
RESULTS
The supplementation of the diet of animals with genistein resulted in an increase in the excretion of methylated derivatives in the urine of rats. In the animals receiving standard diet, the levels of methyl derivatives increased during the study or remained relatively low. In the case of animals whose diet was supplemented with the various forms of genistein, the levels of methylated derivatives were very high from the beginning.
CONCLUSION
High levels of methyl derivatives can influence carcinogenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Chromatography, Liquid; Dietary Supplements; Female; Genistein; Mammary Neoplasms, Experimental; Nucleosides; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry
PubMed: 34182481
DOI: 10.21873/invivo.12475 -
Cancer Research Aug 2021Basal-like breast cancers (BLBC) are characterized by defects in homologous recombination (HR), deficient mitotic checkpoint, and high-proliferation activity. Here, we...
Basal-like breast cancers (BLBC) are characterized by defects in homologous recombination (HR), deficient mitotic checkpoint, and high-proliferation activity. Here, we discover CIP2A as a candidate driver of BLBC. CIP2A was essential for DNA damage-induced initiation of mouse BLBC-like mammary tumors and for survival of HR-defective BLBC cells. CIP2A was dispensable for normal mammary gland development and for unperturbed mitosis, but selectively essential for mitotic progression of DNA damaged cells. A direct interaction between CIP2A and a DNA repair scaffold protein TopBP1 was identified, and CIP2A inhibition resulted in enhanced DNA damage-induced TopBP1 and RAD51 recruitment to chromatin in mammary epithelial cells. In addition to its role in tumor initiation, and survival of BRCA-deficient cells, CIP2A also drove proliferative MYC and E2F1 signaling in basal-like triple-negative breast cancer (BL-TNBC) cells. Clinically, high CIP2A expression was associated with poor patient prognosis in BL-TNBCs but not in other breast cancer subtypes. Small-molecule reactivators of PP2A (SMAP) inhibited CIP2A transcription, phenocopied the CIP2A-deficient DNA damage response (DDR), and inhibited growth of patient-derived BLBC xenograft. In summary, these results demonstrate that CIP2A directly interacts with TopBP1 and coordinates DNA damage-induced mitotic checkpoint and proliferation, thereby driving BLBC initiation and progression. SMAPs could serve as a surrogate therapeutic strategy to inhibit the oncogenic activity of CIP2A in BLBCs. SIGNIFICANCE: These results identify CIP2A as a nongenetic driver and therapeutic target in basal-like breast cancer that regulates DNA damage-induced G-M checkpoint and proliferative signaling.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Autoantigens; Breast Neoplasms; Carcinogenesis; Carrier Proteins; Cell Cycle; Cell Line, Tumor; Cell Proliferation; DNA Damage; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Mice; Mice, Knockout; Mice, Transgenic; Mitosis; Mutation; Nuclear Proteins; Proteome; Recombination, Genetic; Signal Transduction
PubMed: 34145035
DOI: 10.1158/0008-5472.CAN-20-3651