-
Cells Apr 2022Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea () extract, polyphenol extract (a mixture of blackberry (),...
Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea () extract, polyphenol extract (a mixture of blackberry (), blackcurrants (), and added resveratrol phytoalexin), Chinese bayberry () extract, and a coffee () extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely and . The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced as well as tumor suppressor genes.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Biomarkers; Coffee; Gene Expression; Mice; Mice, Inbred CBA; MicroRNAs; Polyphenols; TOR Serine-Threonine Kinases
PubMed: 35455979
DOI: 10.3390/cells11081300 -
BMC Complementary and Alternative... Apr 2018Among the processes involved in the breast tumor microenvironment, angiogenesis and inflammation play a central role, and the main factors of these processes are the...
BACKGROUND
Among the processes involved in the breast tumor microenvironment, angiogenesis and inflammation play a central role, and the main factors of these processes are the vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2) and macrophages. Recently, the extract of Euterpe oleracea (açaí), a fruit that is widely found in the Amazon region, already showed antitumorigenic effects in vitro in human breast cancer cell lines. The present study aimed to investigate the effect of açaí on breast cancer using a chemically DMBA (7,12-dimethylbenzanthracene) experimental model.
METHODS
One day after initiation of treatment with açaí, mammary carcinogenesis was induced in female Wistar rats using a subcutaneous injection of 25 mg/kg of DMBA in the mammary gland. Forty rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 16 consecutive weeks. After treatment, the tumor was collected for macroscopic, histological and immunohistochemical (VEGF, vascular endothelial growth factor receptor 2 -VEGFR-2, COX-2 and matrix metalloproteinase -MMP-9) analyses; peritoneal fluid was subjected to flow cytometry (F4-80/MAC-2+) and ELISA immunoassay (VEGF, prostaglandin E -PGE and interleukin-10 -IL-10). Heart, liver and kidney samples were collected for histological analysis.
RESULTS
After 16 weeks of induction, the mammary carcinoma was confirmed by macroscopic and histological evaluation. Survival analysis indicates that açaí increased the survival (P = .0002, long-rank test) and reduced the deaths number (P = .0036, Chi-square test). Açaí treatment decreased the number of inflammatory cells and macrophage positive cells (Mac-2 + F4-80+), as well as promoting a reduction in immunostaining of VEGF, VEGFR-2 and COX-2. The açaí group also exhibited lower concentrations of PGE, VEGF and IL-10 compared to the control. The histopathological results of the liver and kidneys showed protective effect of açaí, since in the control group, there was an increase in fibrosis, atypical cells and hemorrhagic microenvironment.
CONCLUSION
The results of this study demonstrated the antiangiogenic and anti-inflammatory potential of açaí, like due to the decreases of the number of activated macrophages, resulting in the inhibition of DMBA carcinogenicity in breast cancer.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Carcinogens; Cell Line, Tumor; Euterpe; Female; Humans; Mammary Neoplasms, Experimental; Plant Extracts; Rats; Rats, Wistar
PubMed: 29609579
DOI: 10.1186/s12906-018-2183-z -
The Journal of Toxicological Sciences May 1995Radiosensitization of mice by dimethylbenzanthracene, diphenylcyclopropenone and aminoanthraquinones was investigated in a model where survival time after lethal...
Radiosensitization of mice by dimethylbenzanthracene, diphenylcyclopropenone and aminoanthraquinones was investigated in a model where survival time after lethal radiation was scored. Survival time was shortened by nontoxic doses of the chemicals. The used in vivo system confirmed the radiosensitizing potential of dimethylbenzanthracene reported previously with in vitro studies. Moreover, radiosensitizing properties of diphenylcyclopropenone and aminoanthraquinones could be demonstrated. The sensitizing interaction of these chemicals with radiation adds a new facet to their toxicological spectrum and could, by enhancing radiation effects, influence estimates of risk. On the other hand, diphenylcyclopropenone or aminoanthraquinones deserve consideration as topical sensitizers in conditions where radiation is indicated to treat cutaneous malignancies.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthraquinones; Cyclopropanes; Female; Gamma Rays; Mice; Mice, Inbred C3H; Radiation Injuries, Experimental; Radiation-Sensitizing Agents; Survival Rate
PubMed: 7473893
DOI: 10.2131/jts.20.149 -
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 -
Environmental Health Perspectives Sep 1986The SENCAR mouse stock was selectively bred for eight generations for sensitivity to skin tumor induction by the two-stage tumorigenesis protocol using... (Comparative Study)
Comparative Study Review
The SENCAR mouse stock was selectively bred for eight generations for sensitivity to skin tumor induction by the two-stage tumorigenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The SENCAR mouse was derived by crossing Charles River CD-1 mice with skin-tumor-sensitive mice (STS). The SENCAR mice are much more sensitive to both DMBA tumor initiation and TPA tumor promotion than CD-1, BALB/c, and DBA/2 mice. An even greater difference in the sensitivity to two-stage skin tumorigenesis is apparent between SENCAR and C57BL/6 mice when using DMBA-TPA treatment. However, the SENCAR and C57BL/6 mice have a similar tumor response to DMBA-benzoyl peroxide treatment, suggesting that TPA is not an effective promoter in C57BL/6 mice. The DBA/2 mice respond in a similar manner to the SENCAR mice when using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-TPA treatment. The SENCAR mouse model provides a good dose-response relationship for many carcinogens used as tumor initiators and for many compounds used as tumor promoter. When compared to other stocks and strains of mice, the SENCAR mouse has one of the largest data bases for carcinogens and promoters.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma; Disease Models, Animal; Drug Evaluation, Preclinical; Methylnitronitrosoguanidine; Mice; Mice, Inbred Strains; Papilloma; Skin Neoplasms; Species Specificity; Tetradecanoylphorbol Acetate
PubMed: 3096709
DOI: 10.1289/ehp.866827 -
Cancer Prevention Research... Jan 2015The stress-related catecholamine hormones and the α- and β-adrenergic receptors (α- and β-AR) may affect carcinogenesis. The β-AR GRK/β-arrestin biased agonist...
The stress-related catecholamine hormones and the α- and β-adrenergic receptors (α- and β-AR) may affect carcinogenesis. The β-AR GRK/β-arrestin biased agonist carvedilol can induce β-AR-mediated transactivation of the EGFR. The initial purpose of this study was to determine whether carvedilol, through activation of EGFR, can promote cancer. Carvedilol failed to promote anchorage-independent growth of JB6 P(+) cells, a skin cell model used to study tumor promotion. However, at nontoxic concentrations, carvedilol dose dependently inhibited EGF-induced malignant transformation of JB6 P(+) cells, suggesting that carvedilol has chemopreventive activity against skin cancer. Such effect was not observed for the β-AR agonist isoproterenol and the β-AR antagonist atenolol. Gene expression, receptor binding, and functional studies indicate that JB6 P(+) cells only express β2-ARs. Carvedilol, but not atenolol, inhibited EGF-mediated activator protein-1 (AP-1) activation. A topical 7,12-dimethylbenz(α)anthracene (DMBA)-induced skin hyperplasia model in SENCAR mice was utilized to determine the in vivo cancer preventative activity of carvedilol. Both topical and oral carvedilol treatment inhibited DMBA-induced epidermal hyperplasia (P < 0.05) and reduced H-ras mutations; topical treatment being the most potent. However, in models of established cancer, carvedilol had modest to no inhibitory effect on tumor growth of human lung cancer A549 cells in vitro and in vivo. In conclusion, these results suggest that the cardiovascular drug carvedilol may be repurposed for skin cancer chemoprevention, but may not be an effective treatment of established tumors. More broadly, this study suggests that β-ARs may serve as a novel target for cancer prevention.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Adrenergic beta-Antagonists; Animals; Anticarcinogenic Agents; Atenolol; Carbazoles; Carvedilol; Cell Adhesion; Cell Line; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Isoproterenol; Mice; Mutation; Neoplasm Transplantation; Propanolamines; Skin Neoplasms; Transcription Factor AP-1
PubMed: 25367979
DOI: 10.1158/1940-6207.CAPR-14-0193 -
Nature Communications Oct 2014Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by mechanisms that are not well...
Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by mechanisms that are not well understood. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), cisplatin and etoposide induce nuclear DNA leakage into the cytosol that intrinsically activates stimulator of interferon genes (STING)-dependent cytokine production. Inflammatory cytokine levels are subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING(-/-) mice, or wild-type mice adoptively transferred with STING(-/-) bone marrow, are almost completely resistant to DMBA-induced skin carcinogenesis compared with their wild-type counterparts. Our data establish a role for STING in the control of cancer, shed significant insight into the causes of inflammation-driven carcinogenesis and may provide a basis for therapeutic strategies to help prevent malignant disease.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Cytokines; Exodeoxyribonucleases; Female; Humans; Membrane Proteins; Mice; Mice, Knockout; Phosphoproteins; Skin Neoplasms
PubMed: 25300616
DOI: 10.1038/ncomms6166 -
The Journal of Nutrition Dec 2005Dietary exposures during childhood may influence later breast cancer risk. We tested in an animal model the hypothesis that prepubertal intake of (n-3) PUFAs, present... (Review)
Review
Dietary exposures during childhood may influence later breast cancer risk. We tested in an animal model the hypothesis that prepubertal intake of (n-3) PUFAs, present mainly in fish, reduces susceptibility to breast cancer. Between postnatal days 5 to 25, rat pups were fed (n-3) PUFA-containing diets at a 2:1 ratio of (n-6):(n-3) PUFAs (typical of prehistoric societies) or a control (n-6) PUFA diet at a 17:1 ratio of (n-6):(n-3) PUFAs (comparable with current Western societies). These fatty acids were given in a low- or high-fat context (16 or 39% energy from fat). The low-(n-3) PUFA diet reduced while the high-(n-3) PUFA diet increased carcinogen-induced mammary tumorigenesis. The low-(n-3) PUFA diet reduced mammary cell proliferation and increased apoptosis, particularly in the terminal end buds (the mammary source of malignant breast tumors). The high-(n-3) PUFA diet had opposite effects on these 2 key biomarkers and increased phospho-Akt levels, a survival factor. Microarray analyses identified genes that were permanently upregulated in the low-(n-3) PUFA-exposed glands and function in oxidative damage repair. Serum levels of 8-hydroxy-2'deoxyguanosine, a marker of DNA damage, were significantly reduced in these low-(n-3) PUFA-fed rats, and increased in the high-(n-3) PUFA-exposed group. The latter group exhibited reduced expression of BRCA1, a DNA repair gene. Our results indicate that the opposing susceptibilities to mammary tumorigenesis between the low- versus high-fat (n-3) PUFA-exposed groups were associated with altered DNA damage repair and gene expression linked to proliferation, survival, and differentiation.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Breast Neoplasms; Carcinogens; Diet; Fatty Acids, Unsaturated; Female; Humans; Mammary Neoplasms, Experimental; Rats
PubMed: 16317153
DOI: 10.1093/jn/135.12.2946S -
Cancer Treatment and Research... 2022The current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch...
PURPOSE
The current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch (HBP) carcinogenesis.
MATERIAL AND METHODS
In this study we used 40 Syrian male hamsters, five weeks old, were divided into 4 groups (GI, GII, GIII, and GIV) of 10 animals in each as follows, GI: Topical application of liquid paraffin alone (thrice a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5% in liquid paraffin, thrice a week for 14 weeks), GIII: Topical application of DMBA (0.5% in liquid paraffin, thrice a week for 14 weeks) + Oral administration of DHA (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks on alternative days of DMBA application), GIV: Oral administration of DHA alone (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks).
RESULTS
Gross observations and histopathological findings revealed that, in GI: normal stratified squamous epithelium, in GII: well and moderately differentiated squamous cell carcinoma (SCC), in GIII: variable results ranges from hyperkeratosis, hyperkeratosis and focal hyperplasia, mild dysplasia, and well differentiated SCC with superficial invasion of tumor cells not extended to deeper areas, while in GIV: normal similar to GI. Immunohistochemical results indicated that oral DHA treatment to DMBA treated hamsters restored the normal expression of bcl-2.
CONCLUSION
Our results indicated that DHA has the potential to be a dietary chemopreventive agent due to its capacity to improve carcinogen detoxification and to block/suppress the initiation and promotion stages of experimentally produced HBP carcinogenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinoma, Squamous Cell; Cricetinae; Docosahexaenoic Acids; Humans; Lipid Peroxidation; Male; Mesocricetus; Mineral Oil; Mouth Mucosa; Mouth Neoplasms; Water
PubMed: 35443225
DOI: 10.1016/j.ctarc.2022.100558 -
Experimental Animals Aug 2019Serous borderline ovarian tumors (SBOTs) behave between benign cystadenomas and carcinomas, and the effective detection and clinical management of SBOTs remain clinical...
Serous borderline ovarian tumors (SBOTs) behave between benign cystadenomas and carcinomas, and the effective detection and clinical management of SBOTs remain clinical challenges. Because it is difficult to isolate and enrich borderline tumor cells, a borderline animal model is in need. 7,12-dimethylbenz[a]anthracene (DMBA) is capable of inducing the initiation, promotion, and progression of serous ovarian tumors. This study aims to investigate the proper dosage and induction time of DMBA for rat models of SBOTs, and explore their morphological features demonstrated by magnetic resonance (MR) imaging and molecular genetic characteristics. Rats were randomly divided into six groups (1 mg/70 D, 2 mg/70 D, 3 mg/70 D, 2 mg/50 D, 2 mg/90 D, and 2 mg/110 D). The 3 mg/70 D group induced the most SBOTs (50.0%, 12/24). The micropapillary projections were shown on MR imaging, which was the characteristic of SBOTs. The Cyclin D1 characterizing an early pathogenetic event strongly expressed in induced serous benign tumors (SBTs). The immunoreactivity staining scores of P53 expression significantly increased from SBTs, SBOTs to serous ovarian carcinomas (SCAs), which elucidate that P53 might be a promising biomarker to grade serous ovarian tumors. Based on morphological and molecular genetic similarities, this rodent SBOT model was suitable for investigating the pathogenesis of serous ovarian tumors and developing an early detection strategy.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ovarian Neoplasms; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 30760660
DOI: 10.1538/expanim.18-0103